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>
Acute and subchronic effects of methylenedioxymethamphetamine [(+/-)MDMA] on locomotion and serotonin syndrome behavior in the rat.
Male; Time Factors; Animals; Rats; Behavior; Motor Activity/*drug effects; Amphetamines/*pharmacology; Designer Drugs/*pharmacology; Dose-Response Relationship; Drug; Inbred Strains; Receptors; 3; Animal/*drug effects; N-Methyl-3; 4-methylenedioxyamphetamine; 4-Methylenedioxyamphetamine/analogs & derivatives/*pharmacology; Serotonin/*drug effects
Specific behaviors comprising the serotonin syndrome (low body posture, forepaw treading, headweaving) and the autonomic signs of piloerection and salivation were determined and analyzed with locomotor activity in response to MDMA at three doses (2.5, 5.0, and 7.5 mg/kg). All behaviors were dose-responsive. Serotonin syndrome behaviors increased in both intensity and duration of response with increasing doses. In contrast, locomotion varied only in intensity. Subchronic injections, in the same group of animals, permitted an analysis of acute vs. subchronic effects on these same behaviors. Both the serotonin syndrome and locomotor behaviors were augmented on subsequent testing, indicating that, (+/-)MDMA, like amphetamine, is capable of producing behavioral sensitization.
Spanos L J; Yamamoto B K
Pharmacology, biochemistry, and behavior
1989
1989-04
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/10.1016/0091-3057(89)90044-0" target="_blank" rel="noreferrer noopener">10.1016/0091-3057(89)90044-0</a>
Serotonergic-dopaminergic mediation of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy").
Male; Time Factors; Animals; Rats; Dopamine Agents/*pharmacology; Discrimination (Psychology)/*drug effects; Serotonin/*physiology; *Dopamine Antagonists; Serotonin Antagonists/*pharmacology; Amphetamines/*pharmacology; Dose-Response Relationship; Drug; Inbred Strains; 3; N-Methyl-3; Stimulus; 4-methylenedioxyamphetamine; 4-Methylenedioxyamphetamine/analogs & derivatives/*pharmacology; *Generalization
A series of three experiments were conducted to investigate the possible serotonergic and dopaminergic mediation of the discriminative stimulus properties of the "designer" drug MDMA. In Experiment 1, rats trained to discriminate 1.5 mg/kg (+/-)-MDMA from its vehicle at 20 min postadministration were shown to generalize to another drug of abuse, N-ethyl-3,4-methylenedioxyamphetamine (MDE) and to the serotonergically-active agents norfenfluramine and TFMPP. In contrast, testing of various dopaminergically-active agonists did not result in MDMA-like responding. In Experiment 2, dopaminergic and serotonergic antagonist were employed to observe their effect upon MDMA discrimination at 20 min postinjection. The serotonin antagonist pirenperone significantly decreased MDMA discrimination, whereas the dopamine decreasing drugs CGS 10746B and haloperidol had no effect. In Experiment 3, another group of rats were trained to discriminate MDMA at 105 min postadministration to investigate if, at this (later) time, the dopaminergic properties of MDMA may be more salient. Indeed, the dopaminergically-active drugs had a heightened effect upon MDMA at this later time, although the serotonergic component of the MDMA discriminative stimulus was predominant. The results suggest that the effects of MDMA at 20 min postadministration are solely serotonergic in nature. At 105 min postinjection there appears to be the presence of a weak dopaminergic component. This biphasic serotonergic-then-dopaminergic action of MDMA may explain the reported human experience with the drug, as well as the often controversial results in the literature.
Schechter M D
Pharmacology, biochemistry, and behavior
1988
1988-12
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/10.1016/0091-3057(88)90390-5" target="_blank" rel="noreferrer noopener">10.1016/0091-3057(88)90390-5</a>
Advantages and disadvantages of a rapid method to train drug discrimination.
Male; Animals; Rats; Drug Tolerance; Methods; Discrimination Learning/*drug effects; Amphetamines/*pharmacology; Dose-Response Relationship; Drug; 3; N-Methyl-3; 4-methylenedioxyamphetamine; 4-Methylenedioxyamphetamine/analogs & derivatives/*pharmacology
In an effort to reduce the often extensive period of time needed to train rats to discriminate between a drugged and nondrugged state, a fast training regimen was employed with 1.5 mg/kg 3,4-methylenedioxymethamphetamine (MDMA) used as the training drug in ten rats. This protocol consisted of one to three training sessions per day and it was compared to the more conventional method of once-per-day training in an equal number of rats. Results indicate that the fast-trained rats learned the discrimination in significantly fewer sessions than the slowly-trained rats. However, the subsequent dose-response experiments indicate that when the fast-trained rats are tested with various doses of MDMA, without prior vehicle treatment, their sensitivity to the drug is less than that of the slowly-trained rats. When a vehicle session is presented prior to drug dose-response testing, both groups perform similarly. It appears that the preceding vehicle sessions function as a reference point for the fast-trained rats and, although the more rapid training regimen allows for faster learning, these treatment regimens should be employed with caution when subsequent dose-response tests and generalization tests with other drugs are conducted.
Schechter M D
Pharmacology, biochemistry, and behavior
1988
1988-09
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/10.1016/0091-3057(88)90340-1" target="_blank" rel="noreferrer noopener">10.1016/0091-3057(88)90340-1</a>
The antinociceptive effects of 3,4-methylenedioxymethamphetamine (MDMA) in the rat.
Male; Animals; Rats; Analgesics/*pharmacology; Methysergide/pharmacology; Naltrexone/pharmacology; Amphetamines/*pharmacology; Pain/*metabolism; Morphine/pharmacology; Dose-Response Relationship; Drug; Inbred Strains; Receptors; 3; N-Methyl-3; 4-methylenedioxyamphetamine; 4-Methylenedioxyamphetamine/analogs & derivatives/*pharmacology; Serotonin/drug effects/*physiology
The antinociceptive effects of MDMA and morphine were examined in rats using the tail-flick and hot-plate analgesiometric tests. MDMA, in the dose range of 1.5-6.0 mg/kg IP, produced a dose-dependent elevation in hot-plate latency, but did not elevate tail-flick latency. In contrast, morphine (2-8 mg/kg, IP) produced analgesia on both the tail-flick and hot-plate tests in a dose-dependent manner. Neither the opiate antagonist naltrexone nor the adrenoceptor antagonist phentolamine effectively attenuated MDMA-induced analgesia. Conversely, the serotonin antagonist methysergide significantly reversed the analgesic effects of MDMA on the hot-plate test. These findings suggest that the antinociceptive effects of MDMA are serotonergically mediated. Furthermore, the results verify earlier findings describing the test-specific effects of serotonin-induced pain modulation.
Crisp T; Stafinsky J L; Boja J W; Schechter M D
Pharmacology, biochemistry, and behavior
1989
1989-11
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/10.1016/0091-3057(89)90547-9" target="_blank" rel="noreferrer noopener">10.1016/0091-3057(89)90547-9</a>
Behavioral effects of N-ethyl-3,4-methylenedioxyamphetamine (MDE; "EVE").
Male; Time Factors; Animals; United States; Rats; Discrimination (Psychology); Amphetamines/*pharmacology; Dose-Response Relationship; Drug; Inbred Strains; 3; N-Methyl-3; 4-methylenedioxyamphetamine; 4-Methylenedioxyamphetamine/analogs & derivatives/*pharmacology; Legislation
Eight male rats were trained to discriminate 2.0 mg/kg
Boja J W; Schechter M D
Pharmacology, biochemistry, and behavior
1987
1987-10
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/10.1016/0091-3057(87)90206-1" target="_blank" rel="noreferrer noopener">10.1016/0091-3057(87)90206-1</a>