Reinstatement of cocaine seeking induced by drugs, cues, and stress in adolescent and adult rats.
BACKGROUND
In human and animal studies, adolescence marks a period of increased vulnerability to the initiation and subsequent abuse of drugs. Adolescents may be especially vulnerable to relapse, and a critical aspect of drug abuse is that it is a chronically relapsing disorder. However, little is known of how vulnerability factors such as adolescence are related to conditions that induce relapse, triggered by the drug itself, drug-associated cues, or stress.


OBJECTIVE
The purpose of this study was to compare adolescent and adult rats on drug-, cue-, and stress-induced reinstatement of cocaine-seeking behavior.


METHODS
On postnatal days 23 (adolescents) and 90 (adults), rats were implanted with intravenous catheters and trained to lever press for i.v. infusions of cocaine (0.4 mg/kg) during two daily 2-h sessions. The rats then self-administered i.v. cocaine for ten additional sessions. Subsequently, visual and auditory stimuli that signaled drug delivery were unplugged, and rats were allowed to extinguish lever pressing for 20 sessions. Rats were then tested on cocaine-, cue-, and yohimbine (stress)-induced cocaine seeking using a within-subject multicomponent reinstatement procedure.


RESULTS
Results indicated that adolescents had heightened cocaine seeking during maintenance and extinction compared to adults. During reinstatement, adolescents (vs adults) responded more following cocaine- and yohimbine injections, while adults (vs adolescents) showed greater responding following presentations of drug-associated cues.


CONCLUSIONS
These results demonstrated that adolescents and adults differed across several measures of drug-seeking behavior, and adolescents may be especially vulnerable to relapse precipitated by drugs and stress.
Anker
Justin J
JJ
Department of Psychiatry, University of Minnesota, MMC 392, Minneapolis, MN 55455, USA. anke0022@umn.edu
Carroll
Marilyn E
ME
D000367:Age Factors; D019969:Amphetamine-Related Disorders / Q000523:psychology*; D000818:Animals; D016739:Behavior, Addictive / Q000523:psychology*; D001522:Behavior, Animal / Q000187:drug effects*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage*; D003042:Cocaine / Q000008:administration & dosage*; D003216:Conditioning, Operant; D003463:Cues; D004195:Disease Models, Animal; D005108:Extinction, Psychological; D007262:Infusions, Intravenous; D008297:Male; D010775:Photic Stimulation; D051381:Rats; D017208:Rats, Wistar; D012008:Recurrence; D012646:Self Administration; D013315:Stress, Psychological / Q000139:chemically induced / Q000150:complications*; D013997:Time Factors; D015016:Yohimbine
D000697:Central Nervous System Stimulants; D015016:Yohimbine; D003042:Cocaine