THE CENTRAL NUCLEUS OF THE AMYGDALA CONTRIBUTES TO THE PRODUCTION OF MORPHINE ANTINOCICEPTION IN THE RAT TAIL-FLICK TEST

Current models of endogenous pain control circuitry emphasize neural s ubstrates within the brainstem and spinal cord. We have recently shown , however, that the central nucleus of the amygdala (Ce) contributes t o morphine-induced suppression of formalin-induced nociceptive behavio rs. In the four experiments reported here, we investigated the possibi lity that the Ce also contributes to morphine-induced suppression of s imple, spinally mediated nociceptive reflexes. Bilateral N-methyl-D-as partate (NMDA)-induced lesions of the rat Ce, but not bilateral lesion s centered on either the basolateral or medial amygdaloid nucleus, abo lished the antinociception produced by 2.5 mg/kg morphine sulfate in t he noxious heat-evoked tail-flick test. Bilateral Ce lesions also abol ished the antinociception produced by 2 or 4 mg/kg morphine sulfate, b ut a relatively large dose of morphine sulfate (10 mg/kg, s.c.) result ed in partial reinstatement of antinociception. It is unlikely that th ese effects were due to secondary, seizure-induced damage following NM DA injection (e.g., to areas outside the amygdala) since bilateral ina ctivation of the Ce with the local anesthetic lidocaine also reliably attenuated morphine antinociception. It is also unlikely that these ef fects were artifacts of lesion-induced hyperalgesia, since Ce lesions failed to result in reliable thermal hyperalgesia, even at baseline ta il-flick latencies of 10-12 sec. These data are the first to provide d irect evidence that systemically administered morphine requires the in tegrity of a forebrain area in order to suppress spinally mediated noc iceptive reflexes. It is argued that the present results, together wit h recent evidence linking the Ce to the production of several forms of conditioned and unconditioned environmentally induced antinociception , warrant incorporation of the Ce into current models of endogenous pa in control circuitry.