μ-Opioid and N-methyl-D-aspartate receptors in the amygdala contribute to minocycline-induced potentiation of morphine analgesia in rats.

Abstract

The aim of the present study was to investigate the role of the amygdala in the potentiative effect of minocycline, a semisynthetic tetracycline antibiotic, on morphine analgesia in male Wistar rats. We also examined the involvement of the amygdala μ-opioid and N-methyl-D-aspartate (NMDA) receptors in the minocycline-induced potentiation of morphine analgesia. Intraperitoneal administration of morphine (3-9 mg/kg) induced analgesia in a tail-flick test. Bilateral intra-amygdala injection of minocycline (10-20 μg/rat) enhanced the analgesic response of an ineffective dose of morphine (3 mg/kg). Injection of a higher dose of minocycline into the amygdala also induced analgesia. Moreover, bilateral intra-amygdala injection of naloxone (0.5-1.5 µg/rat) reversed minocycline-induced potentiation of morphine analgesia. Pretreatment of animals with NMDA (0.01-0.1 μg/rat, intra-amygdala) also inhibited the potentiative effect of minocycline on morphine response. Bilateral intra-amygdala injection of the same doses of naloxone or NMDA plus morphine had no effect on the tail-flick latency in the absence of minocycline. It can be concluded that the amygdala has a key role in the potentiative effect of minocycline on morphine analgesia. In addition, amygdala opioidergic and glutamatergic mechanisms may be involved, probably through μ-opioid and NMDA receptors, in the modulation of the minocycline-induced potentiation of morphine analgesia in the tail-flick test.