5-HT1A autoreceptor in dorsal raphe nucleus mediates sensitization of conditioned place preference to cocaine in mice experienced with chronic pain

Chronic stress, including chronic neuropathic pain, cannot only induce depressive disorders but also enhance sensitization to addictive drugs. Ample evidence support the implication of the 5-hydroxytryptamine (5-HT) system in the enhanced sensitization to cocaine. However, mechanisms underpinning such an enhancement are still unclear. By using a neuropathic pain model and a combination of behavioral, neurochemical, and western blotting techniques, this study reveals that the mice experienced with chronic neuropathic pain express both depression-like disorders and significant conditioned place preference to cocaine. The conditioned place preference to cocaine and was abolished by administration of the 5-HT1A receptor antagonist into the dorsal raphe nucleus (DRN). The expression of DRN 5-HT1A receptor was upregulated in mice experienced with chronic neuropathic pain. Moreover, such an upregulation was restored by repeated exposure to cocaine. The results reveal that DRN 5-HT1A receptor mediate the sensitization to cocaine in mice experienced with chronic pain and may be used as a new molecular target for therapeutic interventions to drug addiction influenced by chronic stress.