Repeated nicotine exposure enhances responding with conditioned reinforcement.
BACKGROUND
Stimuli associated with a reinforcer (e.g., an addictive drug) can acquire conditioned reinforcing effects. Clinical observations indicate that smoking depends strongly upon conditioned reinforcement (i.e., cues support smoking behavior); however, little is known about the effects of repeated nicotine exposure on these processes.


OBJECTIVE
This study investigated the consequences of prior repeated nicotine exposure on responding with conditioned reinforcement and on the potentiation of conditioned reinforcement by intra-NAc amphetamine infusion.


METHODS
Rats received repeated saline or nicotine injections (0.35 mg/kg; 15 days) and were, following 3 days of withdrawal, trained to associate a tone + light stimulus with water reinforcement for 10 days. Animals were subsequently tested on acquisition of a new instrumental response with conditioned reinforcement (i.e., 14 days after the final nicotine injection). In additional experiments, animals received an infusion of amphetamine (10 microg per side) prior to the conditioned reinforcement test.


RESULTS
Prior repeated nicotine exposure produced a behaviorally specific enhancement of responding with conditioned reinforcement. Furthermore, repeated nicotine pretreatment also augmented the potentiation of conditioned reinforcement by intra-NAc amphetamine.


CONCLUSIONS
These findings demonstrate that prior repeated nicotine exposure augments the control over behavior by a conditioned reinforcer. Such long-lasting alterations in incentive motivational processes produced by repeated nicotine exposure may depend on drug-induced neuroadaptations in dopamine-regulated signaling within limbic-striatal brain regions that could underly persistent and compulsive aspects of addiction.
Olausson
Peter
P
Department of Psychiatry, Laboratory of Molecular Psychiatry, Yale University, 34 Park Street, New Haven, CT 06508, USA.
Jentsch
J David
JD
Taylor
Jane R
JR
D018759:Adrenergic Uptake Inhibitors / Q000008:administration & dosage; D000661:Amphetamine / Q000008:administration & dosage; D000818:Animals; D001522:Behavior, Animal; D003216:Conditioning, Operant / Q000187:drug effects*; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005731:Ganglionic Stimulants / Q000494:pharmacology*; D008297:Male; D009538:Nicotine / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012054:Reinforcement, Psychology
D018759:Adrenergic Uptake Inhibitors; D005731:Ganglionic Stimulants; D009538:Nicotine; D000661:Amphetamine