Title | Protracted time-dependent increases in cocaine-seeking behavior during cocaine withdrawal in female relative to male rats. |
Publication Type | Journal Article |
Year of Publication | 2008 |
Authors | Kerstetter KA, Aguilar VR, Parrish AB, Kippin TE |
Journal | Psychopharmacology (Berl) |
Volume | 198 |
Issue | 1 |
Pagination | 63-75 |
Date Published | 2008 May |
ISSN | 0033-3158 |
Keywords | Animals, Cocaine, Cocaine-Related Disorders, Conditioning, Operant, Cues, Estrous Cycle, Female, Male, Rats, Rats, Sprague-Dawley, Reinforcement Schedule, Self Administration, Sex Characteristics, Substance Withdrawal Syndrome, Time Factors |
Abstract | RATIONALE: Female rats display higher sensitivity to cocaine relative to males under a variety of conditions. Time-dependent increases in cocaine-seeking behavior (as measured by nonreinforced operant responses) during cocaine withdrawal have been reported in male, but not female, rats. OBJECTIVES: The present study determines sex and estrous cycle influences on time-dependent changes in cocaine-seeking behavior. MATERIALS AND METHODS: Male and female Sprague-Dawley rats were reinforced for "active lever" responses by a cocaine infusion (0.50 mg/kg/infusion, i.v., fixed ratio schedule of reinforcement, FR1) followed by a 20-s time-out when reinforcement was not delivered. Infusions were paired with a light + tone conditioned stimulus. Next, rats underwent cocaine withdrawal for 1, 14, 60, or 180 days before testing cocaine-seeking behavior. Each rat was tested for extinction of operant responding, conditioned-cued reinstatement, and cocaine-primed (10 mg/kg, i.p.) reinstatement. RESULTS: Both males and females displayed a time-dependent increase in cocaine-seeking behavior (active lever presses) under extinction of operant responding and conditioned-cued reinstatement conditions after 60 days of cocaine withdrawal. Moreover, cocaine-seeking behavior during extinction of operant responding in females, but not males, remained elevated at 180 days of cocaine withdrawal. Furthermore, females tested during estrus exhibited higher cocaine-seeking behavior under both extinction of operant responding and cocaine-primed reinstatement conditions relative to other rats independent of the duration of cocaine withdrawal. CONCLUSIONS: The effects of reproductive cycle and withdrawal duration on cocaine-seeking behavior are additive and time-dependent increases in cocaine-seeking behavior are more enduring in females than in male rats. |
DOI | 10.1007/s00213-008-1089-8 |
Alternate Journal | Psychopharmacology (Berl.) |
PubMed ID | 18265959 |