Chronic Heroin Self-Administration Desensitizes μ Opioid Receptor-Activated G-Proteins in Specific Regions of Rat Brain

摘要: In previous studies from our laboratory, chronic noncontingent morphine administration decreased mu opioid receptor-activated G-proteins in specific brainstem nuclei. the present study, receptor binding and were examined after heroin self-administration. Rats trained to self-administer intravenous for up 39 d, achieving intake 366 mg. kg(-1). d(-1). opioid-stimulated [(35)S]GTPgammaS [(3)H]naloxone autoradiography performed adjacent brain sections. Agonist-stimulated also other G-protein-coupled receptors, including delta opioid, ORL-1, GABA(B), adenosine A(1), cannabinoid, 5-HT(1A). brains self-administering rats, was observed periaqueductal gray, locus coeruleus, lateral parabrachial nucleus, commissural nucleus tractus solitarius, as previously morphine-treated animals. addition, found thalamus amygdala Despite this decrease mu-activated G-proteins, demonstrated increased several regions self-administration, there a significant G-protein efficiency expressed ratio between agonist-activated binding. No effects on agonist-stimulated any examined. The effect of self-administration mu-stimulated varied highest lowest cortex striatum. These results not only provide potential neuronal mechanisms that may contribute tolerance dependence, but explain why various opioids develop different degrees.