Contributions of prolonged contingent and noncontingent cocaine exposure to enhanced reinstatement of cocaine seeking in rats.
BACKGROUND
Recent evidence suggests that prolonged cocaine self-administration produces escalation in drug-seeking behavior in rats analogous to the increased intake patterns observed in cocaine-dependent individuals. However, the contributions of prolonged access to cocaine taking vs the pharmacologic effects of the consequent increased cocaine exposure on escalation of drug-seeking behaviors have not been investigated.


OBJECTIVE
The present study assessed the effects of these two factors on maintenance of cocaine self-administration and reinstatement of cocaine seeking.


METHODS
Male, Sprague-Dawley rats were trained to self-administer cocaine (0.2 mg/i.v. infusion; FR1) for 1 h per day for 10 sessions followed by short access (1 h/day), contingent long access (6 h/day), or noncontingent long access (1 h contingent + 5 h of yoked cocaine infusions/day; i.e., short access + yoked) to cocaine for 14 daily sessions. All rats underwent extinction training and were subsequently tested for the ability of cocaine-paired cues or a cocaine-priming injection (7.5 mg/kg i.p.) to reinstate extinguished cocaine seeking.


RESULTS
Rats in all groups maintained stable responding for cocaine reinforcement and subsequently showed significant reinstatement of cocaine-seeking behavior. Conditioned-cued reinstatement was enhanced after the contingent long access and short access + yoked cocaine exposure relative to short access cocaine exposure. Conversely, cocaine-primed reinstatement was enhanced after contingent long-access cocaine exposure relative to the other two conditions.


CONCLUSIONS
Enhanced drug seeking produced by prolonged daily cocaine self-administration is due to a combination of behavioral and pharmacological factors. Specifically, conditioned-cued reinstatement is enhanced by increased cocaine intake and cocaine-primed reinstatement is enhanced by increased cocaine taking.
Kippin
Tod E
TE
Department of Neurosciences, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USA.
Fuchs
Rita A
RA
See
Ronald E
RE
D000818:Animals; D003042:Cocaine / Q000008:administration & dosage*; D003213:Conditioning, Psychological / Q000187:drug effects; D003463:Cues; D005106:Exploratory Behavior / Q000187:drug effects; D005108:Extinction, Psychological / Q000187:drug effects*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012054:Reinforcement, Psychology; D012646:Self Administration
D003042:Cocaine