The influence of reinforcing effects of cocaine on cocaine-induced increases in extinguished responding in cynomolgus monkeys
- 56 Downloads
Although reinstatement of extinguished cocaine self-administration is widely used as an animal model of relapse, it is unclear which behavioral effects of the drug stimulus (i.e., unconditioned, discriminative or reinforcing) mediate the increases in responding after extinction.
To examine the influence of experience with cocaine as a reinforcer on the ability of response-independent cocaine injections to increase extinguished responding.
Materials and methods
Effects of noncontingent injections of cocaine (0.01–1.0 mg/kg, i.v.) were assessed in two groups of cynomolgus monkeys, those with extensive histories of cocaine self-administration when responding was maintained under a concurrent fixed ratio (FR) 50 schedule of saline and food presentation (n = 8) and cocaine-naive monkeys (n = 5) responding under an FR 50 schedule of food presentation. In the latter group, the effects of noncontingent cocaine and food (one or five pellets) were examined before and after a brief history of cocaine (0.03 mg/kg/inj) self-administration under an FR 50 schedule.
In the cocaine-experienced subjects responding under a concurrent schedule of saline and food availability, noncontingent cocaine dose-dependently increased injection-lever responding. In the initially cocaine-naive subjects, no dose of cocaine increased extinguished food-maintained responding before or after a brief exposure to cocaine self-administration. In contrast, noncontingent delivery of five food pellets significantly increased extinguished food-maintained responding after cocaine self-administration.
These results support the view that, under self-administration conditions, the discriminative stimulus effects of cocaine play a prominent role in the ability of cocaine to increase extinguished responding.
KeywordsCocaine Extinction Reinstatement Relapse Self-administration Nonhuman primates
This research was supported by National Institute on Drug Abuse grants DA-10584, F31 DA-020281, DA-12460, and DA-16455. The authors acknowledge the excellent technical assistance of Robert Gould, Michelle Icenhower, Ciara McCabe, Susan Nader, and Matthew Dickens.
Matthew L. Banks and Paul W. Czoty have contributed equally to this work.
- Cador M, Isingrini E, Keiflin R (2006) Systemic cocaine can reinstate an instrumental response not directed towards cocaine but previously performed under cocaine. Soc Neurosci Abstract 189:12Google Scholar
- Czoty PW, Gage HD, Nader SH, Reboussin BA, Bounds M, Nader MA (2007) Acquisition of cocaine self-administration does not alter dopamine D2 receptor or transporter availability in rhesus monkeys. J Addiction Med (in press)Google Scholar
- Dews PB, Wenger GR (1977) Rate-dependency of the behavioral effects of amphetamine. In: Thompson T, Dews PB (eds) Advances in behavioral pharmacology, vol 1. Academic, New York, pp 167–227Google Scholar
- Franks GJ, Lattal KA (1976) Antecedent reinforcement schedule training and operant response reinstatement in rats. Anim Learn Behav 4:374–378Google Scholar
- Kelleher RT, Morse WH (1968) Determinants of the specificity of behavioral effects of drugs. Ergeb Physiol Biol Chem Exp Pharmakol 60:1–56Google Scholar
- Skinner BF, Heron WT (1937) Effects of caffeine and Benzedrine upon conditioning and extinction. Psychol Rec 1:340–346Google Scholar
- Stretch R, Gerber RJ, Wood SM (1971) Factors affecting behavior maintained by response-contingent intravenous infusions of amphetamine in squirrel monkeys. Can J Physiol Pharmacol 49:593–598Google Scholar