Pharmacological characterization of the discriminative stimulus propertiesof the phencyclidine analog, N[1-(2-benzo(b)thiophenyl)-cyclohexyl]piperidine

Rationale: Although both cocaine and the phencyclidine analog, BTCP, have d opamine (DA) re-uptake blocking properties, under some conditions their beh avioral effects can be differentiated. Therefore, we examined whether the d iscriminative stimulus (DS) effects of BTCP are different from those of coc aine. Objectives: To compare the effects of monoamine re-uptake blockers, v arying in their in vitro potencies as inhibitors of DA, norepinephrine (NE) , or serotonin re-uptake, in different groups of rats trained to discrimina te either BTCP or cocaine from saline. Additionally, drugs from other pharm acological classes were tested in both groups. Methods: Rats were trained t o discriminate either BTCP (5 mg/kg, i.p.) or cocaine (10 mg/kg, i.p.) from saline under a two-lever FR10 drug discrimination procedure. Results: BTCP and cocaine cross-substituted in BTCP- and cocaine-trained rats. The DA re -uptake blockers, mazindol, indatraline, methylphenidate. GBR12909, and GBR 12935, occasioned dose-related drug-lever (DL) selection both in cocaine- a nd in BTCP-trained rats, with potencies that were significantly correlated. in contrast, the NE re-uptake blockers, nisoxetine, desipramine, and nortr iptyline, produced higher levels of DL selection in BTCP-trained rats than in cocaine-trained rats, a profile like that reported in low-dose cocaine-t rained rats. Drugs from other classes acted similarly in both discriminatio ns. Further, the alpha(1)-adrenergic antagonist prazosin dose dependently b locked the DS effects of the training dose of BTCP, but not of cocaine. Con clusions: The results suggest that the DS effects of BTCP are similar to co caine, and resemble those of a low training dose of cocaine.