Cocaine-seeking produced by experimenter-administered drug injections: dose-effect relationships in rats

Rationale: Relapse to drug taking is a major obstacle to the effective trea tment of cocaine abuse. Animal studies have determined that various drugs a re able to reinstate extinguished drug-taking behavior. Objectives: This st udy was designed to determine whether there is specificity in the ability o f drugs to lead to cocaine-seeking and to compare potency and efficacy of a variety of drug primes. Another objective was to compare the effect of dru gs with a primary dopaminergic mechanism with those having a secondary effe ct on dopaminergic substrates. Methods: Following acquisition of cocaine se lf-administration, the ability of injections of cocaine (5.0-20.0 mg/kg), a mphetamine (0.30-3.0 mg/kg), methylphenidate (2.0-20.0 mg/kg), nicotine (0. 0375-0.60 mg/kg), caffeine (1.25-20.0 mg/kg), morphine (0.10-10.0 mg/kg) or (Delta)9THC (0.3-3.0 mg/kg) to reinstate extinguished drug taking was meas ured. Tests were conducted in a single day and were comprised of three phas es. The first phase consisted of a 60-min period of cocaine self-administra tion. During phase 2, the cocaine solution was replaced with saline and res ponding was extinguished during the next 3-h period. During phase 3, in whi ch saline again was the only solution available for self-administration, re sponding was monitored for 3-8 h following an injection of a drug prime. Re sults: Reinstatement was produced by experimenter-administered injections o f cocaine, amphetamine, methylphenidate and caffeine but not nicotine, morp hine or (Delta)9THC. The potency and efficacy of cocaine, methylphenidate a nd caffeine were comparable, whereas amphetamine was more potent and effica cious. Cocaine seeking occurred primarily during the first hour following t he injection. Conclusions: These findings suggest that cocaine seeking is o nly produced following administration of specific drugs. It is suggested th at effective drug primes are those that produce a discriminative stimulus t hat generalizes to the stimulus produced by the reinforcing effects of coca ine.