Cocaine discrimination is attenuated by isradipine and CGS 10746B.

Title

Cocaine discrimination is attenuated by isradipine and CGS 10746B.

Creator

Schechter M D

Publisher

Pharmacology, biochemistry, and behavior

Date

1993
1993-03

Description

The discriminative stimulus properties of cocaine are thought to be mediated by dopaminergic mechanisms that may be modulated by calcium ion influx and/or interact with 5-hydroxytryptamine3 (5-HT3) receptors. To test these possibilities, rats were trained to discriminate between the stimulus properties of 10.0 mg/kg cocaine and its vehicle in a two-lever, food-motivated operant task. Once trained, rats showed a dose-related decrease in discriminative performance when tested with lower cocaine doses. An analysis of the dose-response curve indicated an ED50 value of 3.04 mg/kg. Pretreatment with the presynaptic dopamine release-inhibiting agent CGS 10746B (20-40 mg/kg) resulted in a dose-related decrease in cocaine discrimination with the highest dose significantly attenuating cocaine discrimination. Pretreatment with 10-30 mg/kg isradipine, a calcium channel blocker, also resulted in a dose-related decrease in cocaine discriminative performance. In contrast to these positive results, pretreatment with the 5-HT3 receptor antagonist MDL 72222 (3.5-7.0 mg/kg), or the same doses of ibogaine, did not significantly affect cocaine discrimination. The results suggest that cocaine controls differential responding in a discriminative stimulus task by mechanisms that involve presynaptic release of dopamine, which may be regulated by neuronal calcium influx through L-type calcium channels.

Subject

Animals; Antipsychotic Agents/*pharmacology; Calcium Channel Blockers/*pharmacology; Cocaine/antagonists & inhibitors/*pharmacology; Conditioning; Discrimination (Psychology)/*drug effects; Dose-Response Relationship; Drug; Ibogaine/pharmacology; Isradipine/*pharmacology; Male; Operant/drug effects; Rats; Serotonin Antagonists/pharmacology; Sprague-Dawley; Thiazepines/*pharmacology; Tropanes/pharmacology

Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

661–664

Issue

3

Volume

44

Citation

Schechter M D, “Cocaine discrimination is attenuated by isradipine and CGS 10746B.,” NEOMED Bibliography Database, accessed October 23, 2021, https://neomed.omeka.net/items/show/3329.

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