Abstract:
RATIONALE:Previous studies from our laboratory and others have indicated a role for the hypothalamo-pituitary-adrenal (HPA) axis in the extinction/reinstatement animal model of cocaine relapse OBJECTIVE:This present study was designed to investigate the potential role for the HPA axis in the cue- and methamphetamine-induced reinstatement of extinguished methamphetamine-seeking behavior by determining the effects of ketoconazole and the corticotropin-releasing hormone (CRF) type 1 receptor antagonist, CP-154,526, on these behaviors. MATERIALS AND METHODS:Male Wistar rats were trained to self-administer methamphetamine (0.03 mg/kg/infusion). The delivery of methamphetamine was paired with the presentation of a tone and the illumination of a house light. Once stable responding was reached, the rats were placed into extinction. The effects of pretreatment with ketoconazole (25, 50, or 100 mg/kg, i.p.) or CP-154,526 (20 or 40 mg/kg, i.p.; 3 micro g, i.c.v) on cue-induced reinstatement were then evaluated. RESULTS:Cue-induced reinstatement was not significantly attenuated by pretreatment with peripherally administered CP-154,526 or by pretreatment with ketoconazole. However, centrally administered CP-154,526 (3 micro g, i.c.v.) significantly attenuated cue-induced reinstatement. In a separate group of rats, CP-154,526 (20 mg/kg, i.p.) attenuated methamphetamine-induced reinstatement (0.12 mg/kg priming infusion); whereas a higher dose (40 mg/kg) was necessary to attenuate reinstatement induced by a priming infusion of 0.24 mg/kg/infusion. Ketoconazole (50 mg/kg) did not affect reinstatement induced by a 0.12 mg/kg priming infusion and, therefore, was not tested at the higher methamphetamine priming dose. CONCLUSIONS:These data suggest an important role for CRF in the cue- and methamphetamine-induced reinstatement of extinguished methamphetamine-seeking behavior.
journal_name
Psychopharmacology (Berl)journal_title
Psychopharmacologyauthors
Moffett MC,Goeders NEdoi
10.1007/s00213-006-0625-7subject
Has Abstractpub_date
2007-02-01 00:00:00pages
171-80issue
2eissn
0033-3158issn
1432-2072journal_volume
190pub_type
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