Neuroimmune Regulation of GABAergic Neurons Within the Ventral Tegmental Area During Withdrawal from Chronic Morphine

• DOI: 10.1038/npp.2015.221
• Publication Date: 2015-07-23T11:01:01Z
• Authors: Anna M W Taylor; Annie Castonguay; Atefeh Ghogha; Pia Vayssiere; Amynah A A Pradhan; Lihua Xue; Sadaf Mehrabani; Juli Wu; Pat Levitt; Mary C Olmstead; Yves De Koninck; Christopher J Evans; Catherine M Cahill
• Keywords: Conditioned place preference; Brain stimulation reward

Opioid dependence is accompanied by neuroplastic changes in reward circuitry leading to a negative affective state contributing addictive behaviors and risk of relapse. The current study presents neuroimmune mechanism through which chronic opioids disrupt the ventral tegmental area (VTA) dopaminergic that contributes impaired behavior. was induced rodents treatment with escalating doses morphine. Microglial activation observed VTA following spontaneous withdrawal from morphine treatment. Opioid-induced microglial resulted an increase brain-derived neurotrophic factor (BDNF) expression reduction function K+Cl− co-transporter KCC2 within GABAergic neurons. Inhibition or interfering BDNF signaling prevented loss Cl− extrusion capacity restored rewarding effects cocaine opioid-dependent animals. Consistent microglial-derived BDNF-induced disruption reward, intra-VTA injection inhibitor cocaine-induced place preference opioid-naïve extracellular gradient undermines GABAA-mediated inhibition, represents opioid treatments can result blunted circuitry. This directly implicates as regulator states, identifying new therapeutic targets for opiate behaviors.