The Actions Of 3-aminopropanephosphinic Acid At Gaba(b) Receptors In Rat Hippocampus
2-hydroxy-saclofen; b receptors; baclofen; brain slices; ca3 pyramidal cells; excitatory transmission; gaba(b) receptors (postsynaptic); gaba(b) receptors (presynaptic); inhibitory transmission; in-vitro; neurons; patch; Pharmacology & Pharmacy; potent; slice recording; synapses; transmission
Lovinger D M; Harrison N L; Lambert N A
European Journal of Pharmacology
1992
1992-02
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1016/0014-2999(92)90390-p" target="_blank" rel="noreferrer noopener">10.1016/0014-2999(92)90390-p</a>
Inhibition Of Striatal Dopamine Transporter Activity By 17 Beta-estradiol
brain; dopamine transporter; estradiol; estrous-cycle; gonadal steroid hormone; h-3 gbr-12935 binding; mptp-induced neurotoxicity; nigrostriatal; nucleus-accumbens; Pharmacology & Pharmacy; progesterone; protein-kinase-c; release; sex-differences; striatal; synaptosome; uptake inhibition; uptake sites
Disshon K A; Boja J W; Dluzen D E
European Journal of Pharmacology
1998
1998-03
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1016/s0014-2999(98)00008-9" target="_blank" rel="noreferrer noopener">10.1016/s0014-2999(98)00008-9</a>
The Local Monoaminergic Dependency Of Spinal Ketamine
(intrathecal); 5-ht (5-hydroxytryptamine; analgesia; antinociception; cord; inhibition; ketamine; neurons; norepinephrine; opiate; opioid receptors; optical isomers; pharmacology; Pharmacology & Pharmacy; rat-brain; receptor; serotonin; tail-flick test
Crisp T; Perrotti J M; Smith D L; Stafinsky J L; Smith D J
European Journal of Pharmacology
1991
1991-03
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1016/0014-2999(91)90101-u" target="_blank" rel="noreferrer noopener">10.1016/0014-2999(91)90101-u</a>
AUTOANALGESIA - BLOCKADE BY YOHIMBINE
Pharmacology & Pharmacy
Chance W T; Schechter M D
European Journal of Pharmacology
1979
1979
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1016/0014-2999(79)90345-5" target="_blank" rel="noreferrer noopener">10.1016/0014-2999(79)90345-5</a>
AN ISOLATED PERFUSED DOG LUNG PREPARATION FOR THE STUDY OF CYCLIC-GMP METABOLISM - EFFECTS OF SODIUM-NITROPRUSSIDE AND OXYGEN
Pharmacology & Pharmacy
Braughler J M; Maron M B
European Journal of Pharmacology
1982
1982
Journal Article or Conference Abstract Publication
n/a
DISSOCIATION OF INCREASES IN CYCLIC-GMP FROM RELAXATION OF ARTERIAL SMOOTH-MUSCLE
Pharmacology & Pharmacy
Braughler J M
European Journal of Pharmacology
1981
1981
Journal Article or Conference Abstract Publication
n/a
POSSIBLE SEROTONERGIC AND DOPAMINERGIC MEDIATION OF THE N-ETHYL-3,4-METHYLENEDIOXYAMPHETAMINE DISCRIMINATIVE STIMULUS
rat; 3; 2; Pharmacology & Pharmacy; dopamine; drug discrimination; fenfluramine; serotonin; quipazine; amphetamine; mde; mdma; p-chlorophenylalanine; pigeons; saline; tfmpp; (3; 4-methylenedioxyamphetamine); 4-methylenedioxymethamphetamine); 4-tetrahydro-beta-carboline; 5-ht (5-hydroxytryptamine; 6-methoxy-1; mde (n-ethyl-3
Eight male rats previously trained to discriminate 2.0 mg/kg N-ethyl-3,4-methylenedioxyamphetamine (MDE) from its vehicle in a two-lever, food motivated task were utilized to characterize the stimulus properties of MDE. The 5-HT receptor agonists 1-(m-trifluoromethylphenyl)piperazine (TFMPP), quipazine and 6-methoxy-1,2,3,4 tetrahydro-beta-carboline were able to generalize to the stimulus produced by MDE. However, the 5-HT receptor agonists m-chlorophenylpiperazine (mCPP), buspirone and norfenfluramine, the dopamine receptor agonist amphetamine, as well as the acetylcholine receptor agonist arecoline did not completely generalize. In addition, the simultaneous administration of norfenfluramine and amphetamine generalized to MDE. Pretreatment with the serotonin receptor antagonists cinanserin and metergoline or the dopamine receptor antagonist haloperidol failed to completely inhibit the discriminative stimulus produced by MDE. Multiple p-chlorophenylalanine (PCPA) pretreatments significantly reduced MDE discrimination, whereas vehicle discrimination was unaffected. Five days following cessation of PCPA pretreatment, MDE discrimination returned to criterion levels and remained at that level. These results suggest that the stimulus produced by MDE involve a complex interaction of various neurotransmitters, with both serotonergic and dopaminergic components.
Boja J W; Schechter M D
European Journal of Pharmacology
1991
1991-09
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1016/0014-2999(91)90277-w" target="_blank" rel="noreferrer noopener">10.1016/0014-2999(91)90277-w</a>
NON-SPECIFICITY OF BEHAVIORAL DESPAIR AS AN ANIMAL-MODEL OF DEPRESSION
Pharmacology & Pharmacy
Schechter M D; Chance W T
European Journal of Pharmacology
1979
1979
Journal Article
<a href="http://doi.org/10.1016/0014-2999(79)90212-7" target="_blank" rel="noreferrer noopener">10.1016/0014-2999(79)90212-7</a>
LACK OF EFFECT OF CHOLINE AND NARCOTIC-ANTAGONISTS UPON APOMORPHINE DISCRIMINATION
Pharmacology & Pharmacy
Schechter M D
European Journal of Pharmacology
1980
1980
Journal Article
<a href="http://doi.org/10.1016/0014-2999(80)90320-9" target="_blank" rel="noreferrer noopener">10.1016/0014-2999(80)90320-9</a>
HALOPERIDOL-INDUCED SUPER-SENSITIVITY TO THE DISCRIMINATION OF APOMORPHINE
Pharmacology & Pharmacy
Schechter M D
European Journal of Pharmacology
1981
1981
Journal Article
<a href="http://doi.org/10.1016/0014-2999(81)90053-4" target="_blank" rel="noreferrer noopener">10.1016/0014-2999(81)90053-4</a>
FENFLURAMINE DISCRIMINATION IN OBESE AND LEAN ZUCKER RATS - SEROTONERGIC MEDIATION OF EFFECT
Pharmacology & Pharmacy
Schechter M D
European Journal of Pharmacology
1986
1986-06
Journal Article
<a href="http://doi.org/10.1016/0014-2999(86)90092-0" target="_blank" rel="noreferrer noopener">10.1016/0014-2999(86)90092-0</a>
BEHAVIORAL INTERACTIONS OF COADMINISTERED AMPHETAMINE AND PENTOBARBITAL
Pharmacology & Pharmacy
Schechter M D
European Journal of Pharmacology
1983
1983
Journal Article
<a href="http://doi.org/10.1016/0014-2999(83)90195-4" target="_blank" rel="noreferrer noopener">10.1016/0014-2999(83)90195-4</a>
The acute effects of methylenedioxymethamphetamine on dopamine release in the awake-behaving rat.
Male; Animals; Rats; Dopamine/*metabolism; Consciousness; Amphetamines/*pharmacology; Brain/drug effects/metabolism; Caudate Nucleus/drug effects/metabolism; Nucleus Accumbens/drug effects/metabolism; Inbred Strains; 3; 4-Dihydroxyphenylacetic Acid/metabolism; N-Methyl-3; 4-methylenedioxyamphetamine; 4-Methylenedioxyamphetamine/analogs & derivatives/*pharmacology
The effects of the recently classified Schedule I amphetamine analog, 3,4-methylenedioxymethamphetamine [+/-)-MDMA) on caudate and nucleus accumbens dopamine release and metabolism were studied by in vivo voltammetry and HPLC with electrochemical detection. Monitored over a 3 h period, the magnitude of increase in dopamine release and the onset of effect were dose-dependent and similar for both brain areas following the 2.5 and 5 mg/kg dose of the drug. However, responses were different for these brain regions using 10 mg/kg of MDMA; the magnitude of increase was greater and the onset of effect more immediate in caudate. Analysis of dopamine and DOPAC tissue content in both caudate and nucleus accumbens verified the voltammetry results. This study provides the first evidence that MDMA induces dopamine release in vivo and that this effect is region, time- and dose-dependent.
Yamamoto B K; Spanos L J
European journal of pharmacology
1988
1988-03
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/0014-2999(88)90564-x" target="_blank" rel="noreferrer noopener">10.1016/0014-2999(88)90564-x</a>
Inhibition of striatal dopamine transporter activity by 17beta-estradiol.
Female; Animals; Rats; Dopamine/metabolism; Neostriatum/*drug effects/metabolism; Dopamine Plasma Membrane Transport Proteins; *Membrane Glycoproteins; *Nerve Tissue Proteins; Estradiol/*pharmacology; *Membrane Transport Proteins; Carrier Proteins/*antagonists & inhibitors; Synaptosomes/*drug effects/metabolism; Sprague-Dawley
Striatal synaptosomes from ovariectomized rats were prepared to examine the effect of 17beta-estradiol on [3H]dopamine uptake. Estradiol inhibited [3H]dopamine uptake in a dose-dependent manner, with an IC50 of 7.2 microM. Use of identical concentrations of progesterone had no effect on [3H]dopamine uptake. The effects of estradiol were exerted by decreasing the affinity of the transporter for dopamine, as revealed by a dose-dependent increase in the Km. The Km values for 0 (control), 10, and 100 microM estradiol were 108+/-11 258+/-44 and 415+/-40 nM, respectively, with each of the three concentrations tested being significantly different among each other. No statistically significant differences were obtained for the Vmax, with values for the three increasing doses being 9.2+/-0.8, 8.3+/-0.5 and 7.3+/-0.8 pmol/min per mg protein. These results demonstrate that estradiol, but not progesterone, inhibits striatal dopamine uptake by decreasing the affinity of the transporter for dopamine. Such a mechanism may serve as one of the bases for the modulatory effects of estradiol upon the nigrostriatal dopaminergic system.
Disshon K A; Boja J W; Dluzen D E
European journal of pharmacology
1998
1998-03
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
Spinal beta-endorphin analgesia involves an interaction with local monoaminergic systems.
Male; Animals; Rats; Adrenergic alpha-Antagonists/pharmacology; Injections; Serotonin Antagonists/pharmacology; Naltrexone/pharmacology; Spinal Cord/*drug effects; Biogenic Monoamines/*physiology; Analgesics/administration & dosage/antagonists & inhibitors/*pharmacology; beta-Endorphin/administration & dosage/antagonists & inhibitors/*pharmacology; Norepinephrine/physiology; Serotonin/physiology; Inbred Strains; Spinal
beta-Endorphin administered intrathecally (i.t.) in rats produced a dose-dependent elevation in tail-flick latency. Naltrexone administered i.t. as a pretreatment reversed the spinal antinociceptive action of beta-endorphin, suggesting that the opioid interacts directly with spinal opiate receptors. Spinal administration of the alpha 1-adrenoceptor antagonist WB-4101 failed to alter the analgesic effects of the opioid, whereas the alpha 2-adrenoceptor antagonist yohimbine completely blocked beta-endorphin-induced elevations in tail-flick latency. Thus, there is an apparent specificity for the alpha
Crisp T; Stafinsky J L; Hess J E; Uram M
European journal of pharmacology
1989
1989-01
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
Possible serotonergic and dopaminergic mediation of the
Male; Animals; Rats; Serotonin/pharmacology; Discrimination Learning/drug effects; Serotonin Antagonists/pharmacology; Motor Activity/drug effects; Designer Drugs/pharmacology; Fenclonine/pharmacology; Inbred Strains; Receptors; 3; N-Methyl-3; 4-methylenedioxyamphetamine; 4-Methylenedioxyamphetamine/*analogs & derivatives/pharmacology; Dopamine/*drug effects; Serotonin/*drug effects
Eight male rats previously trained to discriminate 2.0 mg/kg
Boja J W; Schechter M D
European journal of pharmacology
1991
1991-09
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
Sex differences in extracellular and intracellular calcium-mediated vascular reactivity to vasopressin in rat aorta.
*Sex Characteristics; 1; 3-Pyridinecarboxylic acid; 4-dihydro-2; 6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-; Animals; Aorta/drug effects/*metabolism; Calcium Channel Agonists/*pharmacology; Calcium Channel Blockers/*pharmacology; Calcium/*metabolism; Diltiazem/pharmacology; Dose-Response Relationship; Drug; Female; In Vitro Techniques; Male; Methyl ester/pharmacology; Potassium Chloride/pharmacology; Rats; Simvastatin/pharmacology; Sprague-Dawley; Vasoconstriction/*drug effects; Vasopressins/*metabolism
In rat thoracic aorta, contractile responses to arginine vasopressin are two-fold higher in females than in males. To determine the roles of extracellular and intracellular Ca2+ in this sexual dimorphism in vascular function, vascular reactivity and Ca2+ channel function were examined in thoracic aortae of male and female rats. In the presence of diltiazem (10 microM), maximal contraction to vasopressin was reduced to a greater extent in male (65+/-2%) than in female aortae (38+/-1%). Maximal contractile responses to KCl and Bay K 8644 were similar in male and female aortae. Sensitivity to KCI was slightly but significantly higher in male than in female aorta; in contrast, sensitivity to Bay K 8644 was nearly three-fold higher in males than in females. Removal of the endothelium enhanced sensitivity to KCl similarly in male and female aortae. In the presence of simvastatin (60 microM; an inhibitor of intracellular Ca2+ release), reactivity to vasopressin was reduced substantially in female (42+/-1%) but unaltered in male aortae. Removal of the endothelium enhanced the inhibitory effect of simvastatin in both female (73+/-2%) and male aortae (41+/-2%). These findings demonstrate that male aortae depend more upon extracellular Ca2+ influx, whereas female aortae depend more upon intracellular Ca2+ release for vasopressin-induced contraction.
Eatman D; Stallone J N; Rutecki G W; Whittier F C
European journal of pharmacology
1998
1998-11
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/s0014-2999(98)00700-6" target="_blank" rel="noreferrer noopener">10.1016/s0014-2999(98)00700-6</a>
Discrete versus cumulative dosing in dose-response discrimination studies.
4-methylenedioxyamphetamine/*pharmacology; Animals; Chemical; Cocaine/*pharmacology; Discrimination Learning/*drug effects; Dose-Response Relationship; Drug; Drug Administration Schedule; Drug Evaluation; Male; N-Methyl-3; Preclinical; Rats; Sprague-Dawley; Stimulation
This study describes the results of a 'side-by-side' comparison of two measurement techniques and two dosing regimens in a discrimination study using rats trained to either 10 mg/kg cocaine or 2 mg/kg 3,4-methylenedioxymethamphetamine (MDMA). The measurements employed were either quantal or quantitative; the former an all-or-none correct lever selection measure and the latter a measure of all responses made at the time that the criterion for selection was met. The dosing regimens were either a discrete single injection of lower doses than used in training or a cumulative dose administration sequence, in an ascending order, during one session on two separate occasions. Results indicate that the cumulative dose-response relationships, as indicated by both the slope of the curve or the generated ED50 value, for the discrete and cumulative dose response curves do not significantly differ. In addition, both the quantal and quantitative measurements yield almost identical ED50 values, thus allowing for accurate comparability of drug-discrimination data using different techniques. The present experimentation employed two drugs known to produce heightened response rates which would not allow for behavioral suppression at the highest doses used either in discrete or cumulative regimens. The pharmacokinetics of the two drugs employed in the discrimination tests are considered and discussed in light of the advantages and disadvantages of each of the two methods employed.
Schechter M D
European journal of pharmacology
1997
1997-05
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/s0014-2999(97)85404-0" target="_blank" rel="noreferrer noopener">10.1016/s0014-2999(97)85404-0</a>
Candyflipping': synergistic discriminative effect of LSD and MDMA.
4-methylenedioxyamphetamine/administration & dosage/*pharmacology; Animal/*drug effects; Animals; Behavior; Discrimination Learning/*drug effects; Drug Synergism; Hallucinogens/administration & dosage/*pharmacology; Lysergic Acid Diethylamide/administration & dosage/*pharmacology; Male; N-Methyl-3; Rats; Serotonin Agents/administration & dosage/*pharmacology
The co-administration of D-lysergic acid diethylamide (LSD; 'Acid') and 3,4-methylenedioxymethamphetamine (MDMA; 'Ecstasy'; 'XTC'), has reached a prevalence that has allowed for the street terminology 'candyflipping' to describe the combination. Internet sites indicate a significant enhancement of central effects with their simultaneous use. In this preliminary observation, male Fawn-Hooded rats were trained to discriminate 1.5 mg/kg MDMA and were, subsequently, tested with doses of MDMA (0.15 mg/kg) or LSD (0.04 mg/kg) that each produced a saline-like response. Co-administration of these doses of MDMA and LSD synergized to produce a maximal MDMA-like response. The possible mechanism for synergistic action upon central serotonergic neurons is discussed to explain the observed effect.
Schechter M D
European journal of pharmacology
1998
1998-01
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/s0014-2999(97)01473-8" target="_blank" rel="noreferrer noopener">10.1016/s0014-2999(97)01473-8</a>
The effects of nicotine on dopamine and DOPAC output from rat striatal tissue.
3; 4-Dihydroxyphenylacetic Acid/*metabolism; Amphetamine/pharmacology; Animals; Central Nervous System Stimulants/pharmacology; Corpus Striatum/*drug effects/*metabolism; Dopamine/*metabolism; Dose-Response Relationship; Drug; Ganglionic Stimulants/administration & dosage/*pharmacology; Male; Nicotine/administration & dosage/*pharmacology; Potassium Chloride/pharmacology; Rats; Sprague-Dawley
The effects of varying doses of nicotine infusion upon spontaneous (basal) and subsequent potassium chloride-stimulated dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) output from superfused corpus striatal tissue fragments of male rats were tested. Spontaneous dopamine and DOPAC outputs were increased in response to 1, 5 and 10, but not to 0.1 and 0 (control) microM concentrations of nicotine. Interestingly, the subsequent K+-stimulated (30 mM) dopamine output was completely abolished in preparations infused with the 5 and 10 microM nicotine, but not with the 1 or 0.1 microM nicotine. No overall significant differences in K+-stimulated DOPAC were obtained among the five doses. In experiment 2, the effects of an initial infusion of amphetamine (10 microM), potassium chloride (30 mM), nicotine (10 microM) or normal superfusion medium (control) were compared upon subsequent K+-evoked dopamine release. The amount of dopamine released in response to the second (subsequent) infusion of K+ was significantly greater in the potassium chloride and control conditions versus the nicotine and amphetamine stimulated groups. No overall differences in DOPAC output were observed among the four conditions of experiment 2. These results demonstrate that nicotine can exert differential modulatory effects upon striatal dopaminergic activity as a function of the dose. The augmented levels of DOPAC output along with the abolition of the K+-stimulated dopamine release in response to the 5 and 10 microM nicotine doses suggest that these doses may simultaneously produce an activation of intraneuronal metabolism of dopamine to DOPAC along with an activation of release and inhibition of uptake to diminish stores available for subsequent responses to K+ stimulation.
Dluzen D E; Anderson L I
European journal of pharmacology
1998
1998-01
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/s0014-2999(97)01438-6" target="_blank" rel="noreferrer noopener">10.1016/s0014-2999(97)01438-6</a>
Olanzapine attenuates the reinforcing effects of cocaine.
Animal/*drug effects; Animals; Antipsychotic Agents/administration & dosage/*pharmacology; Behavior; Benzodiazepines; Cocaine/administration & dosage/antagonists & inhibitors/*pharmacology; Conditioning; Dopamine Uptake Inhibitors/administration & dosage/*pharmacology; Dose-Response Relationship; Drug; Food Preferences/drug effects; Male; Olanzapine; Operant/*drug effects; Pirenzepine/administration & dosage/*analogs & derivatives/pharmacology; Rats; Self Administration; Sprague-Dawley
The possibility that the atypical neuroleptic olanzapine can antagonize the ability of cocaine to produce both conditioned place preference and self-administration in rats was investigated. Pre-treatment with olanzapine (3.0, 4.5 mg/kg, but not 1.5 mg/kg) significantly attenuated conditioned place preference produced by cocaine (10 mg/kg). However, the higher dose of olanzapine administered alone resulted in conditioned place aversion. Pre-treatment with olanzapine also produced a dose-dependent decrease in cocaine self-administration (0.33 mg/infusion) under a fixed-ratio 2 schedule of reinforcement. Olanzapine produced a similar dose-responsive attenuation in operant responding for food (fixed-ratio 10) suggesting that olanzapine produces a nonspecific decrease in operant behavior. Pre-treatment with 4.5 mg/kg olanzapine significantly attenuated cocaine-induced hyperactivity, whereas lower olanzapine doses had little effect upon cocaine-induced hyperactivity. These results suggest that pre-treatment with olanzapine is capable of blocking the reinforcing effects of cocaine and illustrates the value of using multiple tests of reinforcement when evaluating the pharmacological effects of newer psychotherapeutic agents.
Meil W M; Schechter M D
European journal of pharmacology
1997
1997-12
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/s0014-2999(97)01351-4" target="_blank" rel="noreferrer noopener">10.1016/s0014-2999(97)01351-4</a>
Discrimination of cocaethylene in rats trained to discriminate between its components.
Animals; Cocaine/*analogs & derivatives/*pharmacology; Discrimination Learning/*drug effects; Dose-Response Relationship; Drug; Ethanol/*pharmacology; Male; Rats
Two groups of eight male Normalized/National Institutes of Health (N/Nih) rats were used in a food-motivated, 2-lever drug discrimination task with one group being trained to discriminate between 10 mg/kg cocaine vs. 1 g/kg ethanol, whereas the second group was trained to discriminate the metabolic product of these two agents, i.e., cocaethylene (10 mg/kg) vs. its saline vehicle. All drugs were administered intraperitoneally and training/testing was conducted 15 min post-injection. Once both groups of animals attained criterion performance, they were each tested in sessions, interspersed with maintenance sessions, with numerous doses of both cocaine and cocaethylene; this resulted in a typical dose-response relationship in each group but indicated that the cocaine-ethanol trained animals were more sensitive to the lower doses of cocaine (as indicated by a decreased ED50 value, i.e., 1.74 mg/kg) when compared to previously trained cocaine-saline animals (ED50 4.22 mg/kg) and, that in both groups, cocaine was significantly more potent than was cocaethylene. Although numerous laboratories have trained drug vs. drug in the drug discrimination paradigm, this is the first study to train animals to discriminate between two drugs which, although having different discriminative properties, form a third psychoactive compound when co-administered. The sensitivity of drug-drug testing vs. drug-saline testing is discussed, as well as the use of these two agents in human abuse.
Schechter M D
European journal of pharmacology
1997
1997-02
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/s0014-2999(96)00876-x" target="_blank" rel="noreferrer noopener">10.1016/s0014-2999(96)00876-x</a>
Effects of a novel dopamine uptake inhibitor upon extracellular dopamine from superfused murine striatal tissue.
Animals; Biological Transport/drug effects; Buffers; Calcium Channels/metabolism; Dopamine Plasma Membrane Transport Proteins/metabolism; Dopamine Uptake Inhibitors/*pharmacology; Dopamine/*metabolism; Extracellular Space/*drug effects/*metabolism; In Vitro Techniques; Male; Methamphetamine/pharmacology; Mice; Neostriatum/*cytology/drug effects; PC12 Cells; Perfusion; Potassium Channel Blockers/pharmacology; Potassium Channels; Potassium Chloride/pharmacology; Rats; Voltage-Gated/antagonists & inhibitors
The dopamine transporter (DAT) plays an important role in substance abuse, schizophrenia, and dopaminergic toxicity associated with the Parkinsonian animal model toxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Accordingly, the DAT serves as a critical component in regulating dopaminergic function in health and disease states. We have been working with a novel cage compound,
Geldenhuys Werner J; Bezuidenhout Lois-May; Dluzen Dean E
European journal of pharmacology
2009
2009-10
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.ejphar.2009.08.012" target="_blank" rel="noreferrer noopener">10.1016/j.ejphar.2009.08.012</a>
The role of the N-terminal and mid-region residues of substance P in regulating functional selectivity at the tachykinin NK1 receptor.
Amino Acid Sequence; Animals; Binding; Calcium Signaling/physiology; CHO Cells; Competitive/drug effects; Cricetinae; Cricetulus; Dose-Response Relationship; Drug; Iodine Radioisotopes; Ligands; Models; Molecular; Molecular Sequence Data; Neurokinin-1/chemistry/drug effects/*metabolism; Rats; Receptors; Substance P/chemistry/drug effects/*physiology
Previous studies have shown that tachykinin peptide ligands of the tachykinin NK1 receptor exhibit functional selectivity with respect to signal activation and desensitization. The differences are most dramatic between the naturally occurring peptides substance P (RPKPQQFFGLM-NH2) and ranatachykinin C (HNPASFIGLM-NH2). To understand the structural features of the peptides that underlie these differences, four peptide analogs have been designed and tested. The analogs were designed to assess the major structural differences between substance P and ranatachykinin C, including the role of the N-terminal Arg and the substitution of the mid-region Glns with Ala and Ser (Q5 replaced with A and/or Q6 replaced with S). Receptor binding, receptor activation of intracellular calcium fluxes, and receptor desensitization of the rat tachykinin NK1 receptor were quantified for each ligand. All of the peptides bound to the rat tachykinin NK1 receptor with high affinity, produced robust calcium signal activation, and led to agonist-induced receptor desensitization. It was found that deletion of the N-terminal Arg of substance P or replacement of either or both Q5 and Q6 altered the functional selectivity of substance P based on the relationship of receptor binding to receptor activation and activation to desensitization. When considered in light of our previously published nuclear magnetic resonance structure data, the data presented herein suggest that the one, five and six positions of the substance P backbone are key structural residues that govern the relative degree of tachykinin peptide-mediated receptor signaling and desensitization.
Perrine Shane A; Beard Debbie J; Young John K; Simmons Mark A
European journal of pharmacology
2008
2008-09
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.ejphar.2008.06.097" target="_blank" rel="noreferrer noopener">10.1016/j.ejphar.2008.06.097</a>
Genetic selection for nicotine activity in mice correlates with conditioned place preference.
*Conditioning; Analysis of Variance; Animals; Female; Inbred Strains; Male; Mice; Movement/*drug effects; Nicotine/*pharmacology; Operant
Genetically heterogenous stock (HS) mice are being used to develop lines which have differential locomotor response to subcutaneously administered (0.75 mg/kg) nicotine. These groups of nicotine-depressed, nicotine-activated or randomly bred control mice were tested as to conditioned place preference using the same dose of nicotine employed to determine their locomotor performance in activity tests. Results indicate that the nicotine-activated mice showed a significantly greater preference to nicotine when compared to the nicotine-depressed mice; this effect was seen in the first generation and continued in the more recently tested third generation. Evidence is offered to support the hypothesis that it is the stimulatory effects of drugs (of abuse) that can be directly correlatable with the strength of their reinforcing effect upon behavior.
Schechter M D; Meehan S M; Schechter J B
European journal of pharmacology
1995
1995-06
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/0014-2999(95)00139-c" target="_blank" rel="noreferrer noopener">10.1016/0014-2999(95)00139-c</a>
Sex differences in nitric oxide-mediated attenuation of vascular reactivity to vasopressin are abolished by gonadectomy.
*Orchiectomy; *Ovariectomy; Acetylcholine/pharmacology; Animals; Aorta; Arginine/analogs & derivatives/pharmacology; Female; In Vitro Techniques; Male; Muscle; Muscle Contraction/drug effects; Nitric Oxide/antagonists & inhibitors/*physiology; omega-N-Methylarginine; Phenylephrine/pharmacology; Potassium Chloride/pharmacology; Rats; Sex Characteristics; Smooth; Sprague-Dawley; Thoracic/drug effects/physiology; Vascular/drug effects/*physiology; Vasopressins/*pharmacology
In the rat thoracic aorta, contractile responses to vasopressin are two-fold higher in females than in males, primarily because nitric oxide-mediated attenuation of contraction is greater in males than in females. To determine the role of the gonadal steroids in this phenomenon, the effects of gonadectomy on nitric oxide and vascular reactivity to vasopressin were examined in thoracic aortae of age-matched intact and gonadectomized male and female rats. Maximal response to vasopressin was markedly higher in gonadectomized-male than in intact-male aortae (2729 +/- 421 vs. 1375 +/- 222 mg/mg ring weight; P \textless 0.01). Inhibition of nitric oxide synthase with NG-methyl-L-arginine (L-NMMA, 250 microM) enhanced maximal response of intact-male (2824 +/- 413 mg/mg ring weight; P \textless 0.01) but not gonadectomized-male aortae (3034 +/- 365 mg/mg ring weight; P \textgreater 0.05). Sensitivity of male aortae to vasopressin was unaffected by gonadectomy or
Stallone J N
European journal of pharmacology
1994
1994-07
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/0014-2999(94)90654-8" target="_blank" rel="noreferrer noopener">10.1016/0014-2999(94)90654-8</a>
Antiepileptics inhibit cortical N-methyl-D-aspartate-evoked [3H]norepinephrine efflux.
Animals; Anticonvulsants/*pharmacology; Dose-Response Relationship; Drug; Female; Male; N-Methylaspartate/*antagonists & inhibitors; Norepinephrine/*metabolism; Rats
The antiepileptic drugs phenytoin, valproic acid and phenobarbital were examined for their ability to inhibit N-methyl-D-aspartate (NMDA)-stimulated [3H]norepinephrine efflux from rat brain cortical slices. All three drugs inhibited efflux at varying concentrations. Valproic acid was the most potent and inhibited efflux at 0.01 mg/ml. Phenytoin and phenobarbital inhibited efflux at 0.1 mg/ml. These results indicate that some antiepileptic drugs are capable of inhibiting NMDA receptor function in the therapeutic range.
Brown L M; Lee Y P; Teyler T J
European journal of pharmacology
1994
1994-03
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/0014-2999(94)90472-3" target="_blank" rel="noreferrer noopener">10.1016/0014-2999(94)90472-3</a>
Conditioned place aversion produced by dopamine release inhibition.
Analysis of Variance; Animal; Animals; Antipsychotic Agents/administration & dosage/*pharmacology; Aversive Therapy; Conditioning (Psychology); Disease Models; Dopamine Antagonists/administration & dosage/*pharmacology; Dose-Response Relationship; Drug; Injections; Intraperitoneal; Male; Motor Activity/*drug effects; Random Allocation; Rats; Sprague-Dawley; Thiazepines/administration & dosage/*pharmacology
CGS 10746B, a dopamine release inhibitor with properties similar to the atypical antipsychotic clozapine, was assessed as to its behavioral properties using spontaneous locomotor activity and the conditioned place preference test. Rats conditioned with interperitoneally administered doses of 1.25, 2.5, 5.0, 10.0, 20.0 or 30.0 mg/kg CGS 10746B showed a conditioned place aversion, whereas only doses of 5.0 mg/kg or greater suppressed locomotor activity. Results are discussed in terms of dopaminergic mediation of conditioned place preference and spontaneous locomotor activity and methodological concerns involved in employing the conditioned place preference test with drugs that produce opposing affective cues.
Schechter M D; Meechan S M
European journal of pharmacology
1994
1994-08
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/0014-2999(94)90329-8" target="_blank" rel="noreferrer noopener">10.1016/0014-2999(94)90329-8</a>
Conditioned place preference produced by the psychostimulant cathinone.
Alkaloids/administration & dosage/*pharmacology; Animals; Central Nervous System Stimulants/administration & dosage/*pharmacology; Choice Behavior/drug effects; Conditioning (Psychology)/drug effects; Dose-Response Relationship; Drug; Habituation; Male; Motor Activity/*drug effects; Psychophysiologic; Rats; Sprague-Dawley
Previous work has indicated that the psychostimulant cathinone produces a location preference in the conditioned place preference task. The present study expanded upon this earlier work by examining the dose-response nature of cathinone-induced conditioned place preference, as well as testing its effect upon spontaneous locomotor activity. At doses ranging from 0.2 to 1.6 mg/kg, cathinone produced a conditioned place preference at all but the lowest dose, and the highest dose but not the lowest dose increased locomotor activity. Results are discussed in terms of dopaminergic mediation of conditioned place preference and the relationship between conditioned place preference and locomotion being subserved by the same neuronal system.
Schechter M D; Meehan S M
European journal of pharmacology
1993
1993-02
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/0014-2999(93)90739-5" target="_blank" rel="noreferrer noopener">10.1016/0014-2999(93)90739-5</a>
Comparison of the behavioral effects of ibogaine from three sources: mediation of discriminative activity.
*Discrimination (Psychology); Animal/*drug effects; Animals; Behavior; Dose-Response Relationship; Drug; Ibogaine/*pharmacology; Male; Rats; Serotonin Receptor Agonists/pharmacology; Sprague-Dawley
Ibogaine is an alkaloid employed for its hallucinatory properties in West Central Africa which has been the subject of alleged efficacy as an aid in the interruption and treatment of chemical dependency. The major sources of the Schedule I agent are: Sigma Chemical Co., the National Institute on Drug Abuse and as NDA International Inc.'s Endabuse. The intent of the present study was to, for the first time, train rats to discriminate the interoceptive stimuli produced by (10 mg/kg, intraperitoneally administered) ibogaine. Once trained, these rats were used to investigate the dose-response effects to ibogaine from each of the three suppliers. In addition, stimulus generalization to the dopamine antagonist CGS 10476B, as well as to the serotonergically active compounds fenfluramine, TFMPP (1-(m-trifluoromethylphenyl)piperazine, DOI (1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane), MDMA (3,4-methylenedioxymethamphetamine), quipazine and LSD, was tested. The results indicate that ibogaine is readily discriminable from its vehicle and that ibogaine from each of the three supplies produced statistically similar discrimination with ED50 values ranging from 2.5 to 3.4 mg/kg. In addition, various doses of the novel drugs tested produced, at best, intermediate ibogaine-appropriate responding and, thus, no drug tested can be considered to generalize to ibogaine-like stimuli. Discussion concerns the multiple actions of ibogaine that have been cited in the scientific literature. The similarity in potency of ibogaine from three potential suppliers should allow for pre-clinical work using any of these research samples to be comparable.
Schechter M D; Gordon T L
European journal of pharmacology
1993
1993-11
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/0014-2999(93)90664-4" target="_blank" rel="noreferrer noopener">10.1016/0014-2999(93)90664-4</a>
Cholinergic disinhibition in area CA1 of the rat hippocampus is not mediated by receptors located on inhibitory neurons.
2-Amino-5-phosphonovalerate/pharmacology; Action Potentials/drug effects; Adenosine/pharmacology; Animals; Baclofen/pharmacology; Carbachol/pharmacology; Cholinergic/*drug effects; Evoked Potentials/drug effects; GABA-A Receptor Antagonists; Hippocampus/*drug effects; In Vitro Techniques; Membrane Potentials/drug effects; Neurons/*drug effects; Parasympathetic Nervous System/*drug effects; Phorbol Esters/pharmacology; Quinoxalines/pharmacology; Rats; Receptors; Synaptic Transmission/physiology
We studied the effects of carbamylcholine (carbachol; CCh) on monosynaptic inhibitory postsynaptic potentials (IPSPs) evoked in the presence of the excitatory amino acid receptor antagonists 6,7-dinitroquinoxaline-2,3-dione (DNQX) and D,L-2-amino-5-phosphonovalerate (APV). CCh (30 microM) blocked late afterhyperpolarizations but did not depress GABAA receptor-mediated fast monosynaptic IPSPs or GABAB receptor-mediated late monosynaptic IPSPs. In the presence of CCh the GABAB receptor agonist (+/- )-baclofen (2 microM) reversibly hyperpolarized pyramidal neurons and depressed monosynaptic IPSPs as under control conditions. Phorbol-12,13-diacetate (PDAc; 10 microM) increased fast and depressed late monosynaptic IPSPs, and prevented depression of IPSPs by baclofen. These results suggest that cholinergic disinhibition in area CA1 of the hippocampus results from decreased synaptic excitation of inhibitory neurons.
Lambert N A; Teyler T J
European journal of pharmacology
1991
1991-10
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/0014-2999(91)90801-v" target="_blank" rel="noreferrer noopener">10.1016/0014-2999(91)90801-v</a>