Cocaine-induced behaviour: dopamine D1 receptor antagonism by SCH 23390 prevents expression of conditioned sensitisation following repeated administration of cocaine.
Repeated administration of cocaine (15 mg/kg) (once a week for 4 weeks, day 1, 7, 14 and 21) in a conditioned environment produced significant hyperactivity and head bobbing effects which showed sensitisation. Pretreatment with the D1 antagonist SCH 23390 (0.05 mg/kg), a dose that blocked d-amphetamine (2.5 mg/kg)-induced hyperactivity, antagonised the locomotor effects of cocaine after the second (day 7), third (day 14) and fourth (day 21) administration of cocaine but not the first day (day 1). Antagonism of head bobbing occurred on all 4 (1, 7, 14 and 21) days of treatment. In contrast, haloperidol (0.1 mg/kg) significantly reduced amphetamine-induced hyperactivity but potentiated the locomotor and stereotypic effects of cocaine, after administration of cocaine on days 1 and 7 and had no effect on cocaine-induced behaviour on days 14 and 21. The results suggest that the locomotor effects and head bobbing produced by cocaine, together with the expression of sensitisation to these effects in the conditioned environment, involve activation of post-synaptic D1 receptors. The potentiation of the effects of cocaine by a small dose of haloperidol may indicate increased release of dopamine due to blockade of pre-synaptic D2 autoreceptors.
Department of Physiology and Pharmacology, Medical School, Queen's Medical Centre, Nottingham, U.K.
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McCreary
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Marsden
D000661:Amphetamine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001552:Benzazepines / Q000494:pharmacology*; D003042:Cocaine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects*; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors*; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D013239:Stereotyped Behavior / Q000187:drug effects
D001552:Benzazepines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D000661:Amphetamine; D003042:Cocaine; D006220:Haloperidol