A COMPARISON OF THE REINFORCING EFFICACY OF PCP, THE PCP DERIVATIVES TCP AND BTCP, AND COCAINE USING A PROGRESSIVE RATIO SCHEDULE IN THE RAT

This study was designed to compare the reinforcing efficacy of PCP (ph encyclidine:phenylcyclohexyl-piperidine) and the PCP-derivatives BTCP (N-[1-(2-benzo(b)thiophenyl)cyclohexyl]piperidine) and TCP (N-[1-(2-th ienyl)cyclohexyl]-piperidine) to that of cocaine, using a progressive ratio schedule of reinforcement (PR). On the PR schedule the number of responses required to obtain an i.v. infusion of drug was escalated w ith each injection until a breaking point was reached when the animal stopped responding. Since BTCP has an affinity for the DA uptake site comparable to that of cocaine, it was hypothesized that BTCP and cocai ne would show similar patterns of self-administration and comparable b reaking points. In contrast, the high affinity of TCP and PCP for the NMDA-ion channel complex suggested that these two compounds would also support comparable self-administration behaviors. Rats were trained t o self-administer i.v. cocaine during daily 5 h sessions under a fixed -ratio-1 (FR1) schedule. Once consistent lever-pressing behavior was e stablished, BTCP, PCP or TCP was substituted for cocaine. Under the FR 1 schedule, BTCP elicited a regular pattern of lever pressing, unlike PCP and TCP. However, under the PR schedule BTCP elicited breaking poi nts comparable to those produced by equivalent doses of cocaine, where as TCP and PCP produced considerably lower breaking points. These resu lts suggest that BTCP has comparable rewarding properties to that of c ocaine, and that like those of cocaine they are most probably mediated through a site of action at the DA transporter. In contrast, the rela tively weak reinforcing efficacy of PCP and TCP would correlate better with their primary site of action on the PCP binding site within the NMDA-ion channel complex.