Development of Mechanical Hypersensitivity in Rats During Heroin and Ethanol Dependence: Alleviation by CRF1 Receptor Antagonism

摘要: Animal models of drug dependence have described both reductions in brain reward processes and potentiation stress-like (or anti-reward) mechanisms, including a recruitment corticotropin-releasing factor (CRF) signaling. Accordingly, chronic exposure to opiates often leads the development mechanical hypersensitivity. We measured paw withdrawal thresholds (PWTs) male Wistar rats allowed limited (short access group: ShA) or extended (long LgA) heroin cocaine self-administration, made dependent on ethanol via vapor (ethanol-dependent group). In self-administering animals, after transition LgA conditions, were reduced around 50% levels observed at baseline, also significantly lower than animals remaining ShA schedule. contrast, under either (1 h) (6 conditions unaltered. Similar rats, ethanol-dependent developed hypersensitivity eight weeks compared non-dependent animals. Systemic administration CRF1R antagonist MPZP alleviated ethanol. The emergence with may thus represent one critical drug-associated negative emotional state driving these substances. These results suggest CRF-regulated nociceptive pathways associated escalation intake dependence. A greater understanding relationships between pain-related states provide insight into mechanisms underlying addiction, as well reveal new treatment opportunities. This article is part Special Issue entitled 'Post-Traumatic Stress Disorder'.