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

Abstract 

Rationale: Relapse to drug taking is a major obstacle to the effective treatment of cocaine abuse. Animal studies have determined that various drugs are able to reinstate extinguished drug-taking behavior. Objectives: This study was designed to determine whether there is specificity in the ability of 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 drugs with a primary dopaminergic mechanism with those having a secondary effect on dopaminergic substrates. Methods: Following acquisition of cocaine self-administration, the ability of injections of cocaine (5.0–20.0 mg/kg), amphetamine (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 ^Δ9THC (0.3–3.0 mg/kg) to reinstate extinguished drug taking was measured. Tests were conducted in a single day and were comprised of three phases. The first phase consisted of a 60-min period of cocaine self-administration. During phase 2, the cocaine solution was replaced with saline and responding was extinguished during the next 3-h period. During phase 3, in which saline again was the only solution available for self-administration, responding was monitored for 3–8 h following an injection of a drug prime. Results: Reinstatement was produced by experimenter-administered injections of cocaine, amphetamine, methylphenidate and caffeine but not nicotine, morphine or ^Δ9THC. The potency and efficacy of cocaine, methylphenidate and caffeine were comparable, whereas amphetamine was more potent and efficacious. Cocaine seeking occurred primarily during the first hour following the injection. Conclusions: These findings suggest that cocaine seeking is only produced following administration of specific drugs. It is suggested that effective drug primes are those that produce a discriminative stimulus that generalizes to the stimulus produced by the reinforcing effects of cocaine.