Injection of minocycline into the periaqueductal gray attenuates morphine withdrawal signs

Abstract

This study investigated the effects of minocycline microinjections, into the midbrain periaqueductal gray (PAG), on morphine withdrawal and the expression of pannexin-1 (panx1), phosphorylated mammalian target of rapamycin (p-mTOR), protein kinase A (PKA), and cAMP response element-binding protein (CREB). Rats were injected with morphine, intraperitoneally, at increasing doses, twice per day, to establish animal models of morphine exposure. Minocycline was administered into the PAG before the first intraperitoneal (i.p.) injection of morphine each day, on days 1–4. On the last day of the experiment, all rats were injected with naloxone, and morphine withdrawal was observed, and then changes in the expression levels of ionized calcium-binding adaptor molecule 1 (Iba1) and its downstream factors, panx1, p-mTOR, PKA, and CREB were evaluated by western blot and immunohistochemistry analyses. Morphine withdrawal increased microglial activation, whereas minocycline could inhibit microglial activation and withdrawal and the downregulation of panx1, p-mTOR, PKA, and CREB expression, reducing the effects of morphine withdrawal.