Conditioned place aversion following the central administration of a novel dopamine release inhibitor CGS 10746B.
Animals; Antipsychotic Agents/administration & dosage/*pharmacology; Avoidance Learning/*drug effects; Dopamine/*metabolism; Inbred Strains; Injections; Intraventricular; Male; Motor Activity/*drug effects; Rats; Thiazepines/administration & dosage/*pharmacology
Numerous drugs of abuse that elevate brain extracellular dopamine concentrations by either increasing the firing rate of dopaminergic neurons or producing dopamine release have been shown to reliably condition a preference for place. If dopamine release is a necessary component for conditioned place preference (CPP), one reciprocal hypothesis may be that inhibition of dopamine release will result in conditioned place aversion (CPA). This hypothesis has been tested pharmacologically by employing CGS 10746B (CGS), a novel neuroleptic known to inhibit the release of dopamine via presynaptic mechanisms. In previous work the peripheral administration of CGS (1.25-20 mg/kg) produced place aversion at doses above 5 mg/kg. However, the contribution of peripheral mechanisms in the production of CGS-induced CPA is unknown. To test whether central administration of CGS would also result in CPA, rats were fitted with chronic intraventricular cannula. Groups of rats subsequently received four conditioning trials with one of four intraventricular (ICV) doses of CGS (1-30 micrograms) when confined to their preferred side of a place conditioning apparatus. Vehicle was similarly administered on four interspersed days prior to confining these same rats to their nonpreferred side of the apparatus. At the conclusion of these eight conditioning trials, the rats were tested, on separate days, in a nondrugged and a CGS-drugged state. The highest dose of CGS (30 micrograms) produced a CPA as evidenced by rats spending less time in the environment initially found to be preferred. Locomotor activity was also measured over a 30-min period with and without ICV injection of CGS (1-30 micrograms).(ABSTRACT TRUNCATED AT 250 WORDS)
Calcagnetti D J; Schechter M D
Pharmacology, biochemistry, and behavior
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/10.1016/0091-3057(91)90548-g" target="_blank" rel="noreferrer noopener">10.1016/0091-3057(91)90548-g</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>