Discriminative stimulus properties of CGS 10746B: similarity to dopamine D1 receptor antagonists.
CGS 10746B is an imidazole-derivative related to the atypical antipsychotic clozapine which produces a decrease in dopamine release without altering dopamine metabolism or occupying D2 receptors. Rats were trained on an appetitively-motivated, two-choice, operant task to discriminate 20.0 mg/kg CGS 10746B from its vehicle. CGS 10746B was highly discriminable, producing rapid acquisition of the discrimination, and its effects were dose-responsive allowing generation of an ED50 value of 6.16 mg/kg. Substitution tests were conducted with other typical and atypical antipsychotic compounds: haloperidol, chlorpromazine, clozapine and SCH 23390. Additional tests examined generalization from the CGS 10746B stimulus properties to the calcium channel blocker isradipine, as well as to the anticholinergics atropine, scopolamine and methylscopolamine, as well as to the serotonergic agonist DOI. Clozapine and SCH 23390 were the only substances to substitute for the CGS 10746B stimulus cue. Results are discussed in terms of potential D1 receptor selectivity of CGS 10746B.
Meehan
S M
SM
Department of Pharmacology, Northeastern Ohio Universities College of Medicine, Rootstown 44266, USA.
Schechter
M D
MD
D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D018678:Cholinergic Agents / Q000494:pharmacology; D003024:Clozapine / Q000494:pharmacology; D003463:Cues; D004193:Discrimination Learning / Q000187:drug effects; D004192:Discrimination, Psychological / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005794:Generalization, Response / Q000187:drug effects; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors*; D018490:Serotonin Agents / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013841:Thiazepines / Q000494:pharmacology*
D000662:Amphetamines; D014150:Antipsychotic Agents; D018678:Cholinergic Agents; D017447:Receptors, Dopamine D1; D018490:Serotonin Agents; D017366:Serotonin Receptor Agonists; D013841:Thiazepines; C049819:CGS 10746B; D003024:Clozapine; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine