Abstract:
RATIONALE:Intermittent footshock stress reliably reinstates extinguished alcohol-taking behavior in drug-free rats, but the neurochemical events involved in this effect are not known. OBJECTIVE:We studied here whether two main modulators of stress responses, corticotropin-releasing factor (CRF) and corticosterone, are involved in reinstatement of alcohol seeking induced by the intermittent footshock stressor. METHDOS: Rats were given alcohol in a two-bottle choice procedure (water versus alcohol) for 30 days and were then trained for 60 min per day to press a lever for alcohol (12% w/v) for 24-30 days in operant conditioning chambers. After stable drug-taking behavior was obtained, lever pressing for alcohol was extinguished by terminating drug delivery for 5-8 days. Reinstatement of alcohol seeking was then determined after exposure to intermittent footshock (0.8 mA; 10 min) in different groups of rats that were pretreated with CRF receptor antagonists or underwent adrenalectomy (ADX) to remove endogenous corticosterone from the body. RESULTS:The CRF receptor antagonists, d-phe-CRF (0.3 or 1.0 microg; ICV) and CP-154,526 (15, 30 or 45 mg/kg; IP) attenuated footshock-induced reinstatement of alcohol seeking in a dose dependent manner. In contrast, the removal of circulating corticosterone by ADX had no effect on footshock stress-induced reinstatement of alcohol-taking behavior. In addition, the prevention of the footshock-induced rise in corticosterone while maintaining basal levels of the hormone by providing adrenalectomized rats with corticosterone pellets (50 mg/kg per day), had no effect on stress-induced reinstatement. CONCLUSIONS:These data suggest that CRF contributes to stress-induced relapse to alcohol seeking via its actions on extra-hypothalamic sites. The present data, and previous data with heroin- and cocaine-trained rats, point to a general role of CRF in relapse to drugs induced by stressors.
journal_name
Psychopharmacology (Berl)journal_title
Psychopharmacologyauthors
Lê AD,Harding S,Juzytsch W,Watchus J,Shalev U,Shaham Ydoi
10.1007/s002130000411subject
Has Abstractpub_date
2000-06-01 00:00:00pages
317-24issue
3eissn
0033-3158issn
1432-2072journal_volume
150pub_type
杂志文章abstract:BACKGROUND AND RATIONALE:Epidemiological evidence suggests that people who begin experimenting with drugs of abuse during early adolescence are more likely to develop substance use disorders (SUDs), but this correlation does not guarantee causation. Animal models, in which age of onset can be tightly controlled, offer ...
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pub_type: 临床试验,杂志文章,随机对照试验
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