Opiate exposure and withdrawal dynamically regulate mRNA expression in the serotonergic dorsal raphe nucleus.

摘要: Previous results from our lab suggest that hypofunctioning of the serotonergic (5-HT) dorsal raphe nucleus (DRN) is involved in stress-induced opiate reinstatement. To further investigate effects morphine dependence and withdrawal on 5-HT DRN system, we measured gene expression at level mRNA during a model dependence, post stress exposure rats. Morphine pellets were implanted for 72h then either removed or animals injected with naloxone to produce spontaneous precipitated withdrawal, respectively. Animals exposed these conditions exhibited symptoms including weight loss, wet dog shakes jumping behavior. Gene brain-derived neurotrophic factor (BDNF), tyrosine kinase receptor B (TrkB), corticotrophin releasing-factor (CRF)-R1, CRF-R2, alpha 1 subunit GABAA (GABAA-α1), μ-opioid (MOR), 5-HT1A receptor, tryptophan hydroxylase2 (TPH2) transporter was using quantitative real-time polymerase chain reaction multiple time-points across exposure, stress. Expression levels BDNF, TrkB CRF-R1 decreased both following 7days withdrawal. CRF-R2 elevated after 3h while TPH2 swim There no changes GABAA-α1, MOR mRNA. Collectively alterations neurotrophin support, CRF-dependent signaling, synthesis release may underlie hypofunction can potentially lead relapse.