1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) disrupts social memory/recognition processes in the male mouse.
*Social Behavior; 1-Methyl-4-phenyl-1; 2; 3; 6-tetrahydropyridine/*analogs & derivatives/pharmacology; Animals; Brain Chemistry/drug effects; Catecholamines/metabolism; Cognition/*drug effects; Dopamine Agents/*pharmacology; Dopamine/metabolism; Habituation; Levodopa/pharmacology; Male; Memory/*drug effects; Mice; Psychophysiologic/drug effects
Male mice treated with MPTP or vehicle were tested for their ability to demonstrate a memory-recognition response as evaluated in a habituation-dishabituation task. Treatment with MPTP severely disrupted the male's habituation-dishabituation response profile compared to vehicle treated animals. Administration of L-DOPA at 45 min prior to behavioral testing in MPTP animals restored their performance on the habituation-dishabituation test to levels observed in vehicle treated animals. There was also a tendency for L-DOPA to produce enhanced responsiveness in vehicle treated animals. Mice treated with MPTP had significantly reduced concentrations of norepinephrine within the olfactory bulb and hippocampus. Vehicle treated mice administered L-DOPA had significantly increased dopamine concentrations within the corpus striatum. These results suggest that, in addition to its putative effects upon the nigrostriatal dopaminergic system and motor behavior, MPTP is also exerting substantial effects upon other systems. In particular, the noradrenergic system and its potential involvement with memory/recognition processes in the CD-1 mouse appears to be very sensitive to the neurotoxic effects of MPTP.
Dluzen D E; Kreutzberg J D
Brain research
1993
1993-04
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/10.1016/0006-8993(93)90860-p" target="_blank" rel="noreferrer noopener">10.1016/0006-8993(93)90860-p</a>
Dose-response effects of estrogen and tamoxifen upon methamphetamine-induced behavioral responses and neurotoxicity of the nigrostriatal dopaminergic system in female mice.
3; 4-Dihydroxyphenylacetic Acid/metabolism; Animal/*drug effects; Animals; Behavior; Brain Chemistry/drug effects; Dopamine/*metabolism; Dose-Response Relationship; Drug; Drug Interactions; Estrogen Antagonists/pharmacology; Estrogens/*pharmacology; Female; Methamphetamine/*toxicity; Mice; Movement/drug effects; Neostriatum/*drug effects/physiology; Neurotoxins/*toxicity; Organ Size/drug effects; Ovariectomy/methods; Stereotyped Behavior/drug effects; Substantia Nigra/drug effects/physiology; Tamoxifen/*pharmacology; Uterus
In the present experiment we evaluated the dose-response effects of estrogen (estradiol benzoate; EB) and tamoxifen (TMX) in modulating the acute behavioral and chronic effects of methamphetamine (MA) upon the nigrostriatal dopaminergic (NSDA) system in ovariectomized (OVX) mice. EB over a range of doses from 1-40 microg resulted in a neuroprotective effect upon the NSDA system as defined by both a preservation of striatal dopamine (DA) concentrations and a decrease in DOPAC/DA ratios. Interestingly, the neuroprotective effect of the 1-microg EB dose occurred in the absence of any statistically significant effect upon the bioassay parameter of uterine weight. With the exception of an increase in stereotypy time as a response to the 40-microg dose, EB at any of the doses tested failed to alter any acute behavioral responses evoked by MA. In response to TMX, a statistically significant NSDA neuroprotectant response was obtained for DOPAC/DA ratios, but not DA concentrations, to doses ranging from 12.5 to 500 microg. No statistically significant effects upon uterine weights were obtained for any of the doses of TMX tested. Behaviorally, TMX at 500 microg had the effect of increasing the amount of time spent in the center of the cage. Taken together these results demonstrate: (1) EB and TMX at relatively low doses can exert a neuroprotective effect against MA; (2) these neuroprotective effects of EB and TMX can occur in the absence of an effect upon the bioassay parameter–uterine weights; (3) the parameter of DOPAC/DA ratio may indicate a more sensitive index of NSDA neuroprotection, and (4) modulatory effects of EB and TMX upon acute behavioral responses of the NSDA system to MA can be distinguished from their neuroprotective actions.
Mickley Katherine R; Dluzen Dean E
Neuroendocrinology
2004
2004
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/10.1159/000079710" target="_blank" rel="noreferrer noopener">10.1159/000079710</a>
Effect of serotonin depletion by p-chlorophenylalanine upon discriminative behaviours.
Male; Animals; Rats; Dopamine/physiology; Brain Chemistry/drug effects; Central Nervous System Stimulants/pharmacology; Discrimination (Psychology)/*drug effects; Serotonin/*physiology; Fenclonine/*pharmacology; Serotonin Antagonists/*pharmacology; Inbred Strains
1. Para-chlorophenylalanine (p-CPA), a competitive inhibitor of the serotonin (5-HT) synthesis enzyme tryptophan hydroxylase, was administered to rats at a dosage (100 mg/kg daily for 3 days) that depletes 5-HT. 2. Different groups of these rats were previously trained to discriminate the interoceptive stimuli produced by amphetamine, cathinone, 3,4-methylenedioxymethamphetamine (MDMA),
Schechter M D
General pharmacology
1991
1905-6
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/10.1016/0306-3623(91)90226-v" target="_blank" rel="noreferrer noopener">10.1016/0306-3623(91)90226-v</a>
Serotonergic mediation of cocaine seizures in mice.
Animals; Brain Chemistry/drug effects; Cinanserin/pharmacology; Cocaine/*toxicity; Epilepsy; Female; Fenfluramine/pharmacology; Inbred Strains; Male; Mice; Seizures/chemically induced/*physiopathology; Serotonin Antagonists/pharmacology; Serotonin Receptor Agonists/pharmacology; Serotonin/*physiology; Status Epilepticus/chemically induced/physiopathology; Tonic-Clonic/chemically induced/physiopathology
We used genetically heterogeneous HS mice to investigate the effects of drugs that alter brain concentrations of serotonin on cocaine-induced convulsions and lethality. The racemer of fenfluramine, which increases synaptic serotonin, was coadministered with a dose (60 mg/kg, intraperitoneally) of cocaine that does not produce status epilepticus or death. This drug combination significantly increased the occurrence and decreased the time of onset of status epilepticus, but did not affect lethality. Likewise, 2.5 mg/kg of the D-isomer, of fenfluramine increased the occurrence of status epilepticus. Neither isomer effected lethality. When 2.5 mg/kg cinanserin, a drug that antagonizes postsynaptic serotonergic receptors, was coadministered with a higher (95 mg/kg) dose of cocaine, the time of onset of status epilepticus was significantly increased, whereas lethality was reduced. The results are discussed in light of the action of cocaine upon serotonin neurons and the relationship between seizurogenic activity and cocaine-induced lethality.
Schechter M D; Meehan S M
Pharmacology, biochemistry, and behavior
1995
1995-07
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/10.1016/0091-3057(94)00386-w" target="_blank" rel="noreferrer noopener">10.1016/0091-3057(94)00386-w</a>