Place-aversion conditioned by phencyclidine in rats: development of tolerance and pharmacologic antagonism.
The pharmacologic properties of phencyclidine were assessed in adult, male rats using a three-chambered, place-conditioning apparatus. Phencyclidine hydrochloride (PCP), at doses of 0.5 to 4 mg/kg, produced a dose-related place-aversion after three drug/environment pairings. During the place-conditioning procedure, 4 mg/kg of PCP significantly increased spontaneous locomotor activity compared to saline-control. Tolerance to PCP-induced place-aversion developed after four daily administrations of 4 mg/kg of PCP. d-Butaclamol, 0.4 mg/kg, given 1 min before each of the three conditioning-doses of PCP decreased the development of the place-aversion induced by PCP. 1-Butaclamol was without significant effect. Spiroperidol, 0.06 mg/kg, completely blocked the development of PCP place-aversion. Spiroperidol and the stereoisomers of butaclamol did not have significant place-conditioning activity when administered alone in the place-conditioning paradigm. The data suggest that PCP induces place-aversion in rats in the place-conditioning model, and that tolerance to this effect develops within 4 days. Furthermore, since d-butaclamol or spiroperidol, but not 1-butaclamol, antagonized this effect of PCP, PCP-induced place-aversion may be mediated in part by a dopaminergic mechanism.
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Iwamoto
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D002069:Butaclamol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010622:Phencyclidine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects; D013134:Spiperone / Q000494:pharmacology; D013237:Stereoisomerism; D013997:Time Factors
D011954:Receptors, Dopamine; D013134:Spiperone; D002069:Butaclamol; D010622:Phencyclidine