Title | Contributions of prolonged contingent and noncontingent cocaine exposure to enhanced reinstatement of cocaine seeking in rats. |
Publication Type | Journal Article |
Year of Publication | 2006 |
Authors | Kippin TE, Fuchs RA, See RE |
Journal | Psychopharmacology (Berl) |
Volume | 187 |
Issue | 1 |
Pagination | 60-7 |
Date Published | 2006 Jul |
ISSN | 0033-3158 |
Keywords | Animals, Cocaine, Conditioning (Psychology), Cues, Exploratory Behavior, Extinction, Psychological, Male, Motor Activity, Rats, Rats, Sprague-Dawley, Reinforcement (Psychology), Self Administration |
Abstract | RATIONALE: 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. |
DOI | 10.1007/s00213-006-0386-3 |
Alternate Journal | Psychopharmacology (Berl.) |
PubMed ID | 16598453 |
Grant List | C06 RR015455 / RR / NCRR NIH HHS / United States DA10462 / DA / NIDA NIH HHS / United States DA15369 / DA / NIDA NIH HHS / United States |