Cocaine-induced reinstatement in rats: evidence for a critical role of cocaine stimulus properties

• Published in: Psychopharmacologia 2008-05, Vol.197 (4), p.649-660
• Main Authors: Keiflin, Ronald, Isingrini, Elsa, Cador, Martine
• Format: Article
• Language: English
• Subjects: Addictions; Animals; Appetitive Behavior; Appetitive Behavior - drug effects; Association Learning; Association Learning - drug effects; Behavior modification; Biochemistry; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Central Nervous System Stimulants; Central Nervous System Stimulants - pharmacology; Cocaine; Cocaine - pharmacology; Discrimination Learning; Discrimination Learning - drug effects; Dose-Response Relationship, Drug; Extinction, Psychological; Extinction, Psychological - drug effects; Injections, Intraperitoneal; Life Sciences; Male; Medical sciences; Mental Recall; Mental Recall - drug effects; Motivation; Motor Activity; Motor Activity - drug effects; Neurology; Neuropharmacology; Neurosciences; Pharmacology. Drug treatments; Pharmacology/Toxicology; Psychiatry; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Rats; Rats, Wistar; Rodents
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-008-1083-1

Rationale The exact behavioral nature of drug-induced reinstatement of drug seeking is still debated. As an incentive, the drug can have general facilitatory influences on appetitive behaviors. As an interoceptive stimulus, the drug can acquire discriminative properties and control behavior. Objective This study assessed the relative contribution of the incentive versus discriminative properties of cocaine in food-seeking reinstatement. Methods In Experiment 1, eight groups of rats were trained to press a lever for food pellets and experienced cocaine (0, 5, 10, or 15 mg/kg; i.p.), either during the operant conditioning sessions or 4 h after, in another environment without food access. In Experiment 2, to dissociate the role of the operant response per se from the consummatory response, two groups of rats experienced food consumption under cocaine (10 mg/kg; i.p.) either during operant conditioning sessions or during alternate sessions of free access to the food. Then, for both experiments, food pellets were withheld and cocaine injections ceased (extinction). The reinstating effects of noncontingent cocaine (10 mg/kg; i.p.) and food pellet delivery were assessed. Locomotor activity was recorded to probe expression of behavioral sensitization. Results Cocaine reinstated lever pressing only in rats having previously performed the operant responses under cocaine. In contrast, food pellet delivery reinstated lever pressing independently of rats’ history with cocaine. Locomotor sensitization was evidenced for all cocaine-pre-exposed rats, dissociating sensitization from reinstatement. Conclusions When present during operant conditioning, the stimulus “cocaine” acquires conditioned properties which can then promote reinstatement of the extinguished behavior.