ANTINOCICEPTIVE EFFECTS OF STIMULATION OF DISCRETE SITES IN THE RAT HYPOTHALAMUS - EVIDENCE FOR THE PARTICIPATION OF THE LATERAL HYPOTHALAMUS AREA IN DESCENDING PAIN SUPPRESSION MECHANISMS

The sites in the rat hypothalamus where microinjection of morphine (5 mu g/0.5 mu l) or electrical stimulation depresses the tail withdrawal reflex to noxious heating of the skin were examined. Among other hypo thalamic sites found to be sensitive to morphine or to an electrical s timulus, the posterior part of the lateral hypothalamic area (LHA) was the only portion of the hypothalamus that was strongly sensitive to b oth manipulations. A 15-sec period of 35-mu A sine-wave stimulation of the LHA significantly increased the latency of the tail reflex for pe riods up to 30 min. The effects of intraperitoneal administration of a ntagonists to opioids (naloxone), 5-hydroxytryptamine (methysergide), noradrenaline (phenoxybenzamine), dopamine (haloperidol), and acetylch oline (atropine and mecamylamine) on the antinociceptive effects of LH A stimulation were also examined. Naloxone, methysergide, and atropine (all given at doses of 0.5 and 1.0 mg/kg) attenuated the effects of L HA stimulation in a dose-dependent manner. Phenoxybenzamine, but not h aloperidol (both at the dose of 1.0 mg/kg), was also effective but dos e-dependent curves could not be constructed. Mecamylamine (1.0 mg/kg) reduced the duration but not the peak effect of stimulating the LHA. W e conclude that antagonism at the level of opioid, serotonergic, adren ergic, and muscarinic cholinergic receptors, but not dopamine or nicot inic cholinergic receptors, reduces the antinociceptive effects of LHA stimulation. This may imply that antinociception evoked from the LHA depends on the activation of descending pathways that relay in the mes encephalic periaqueductal gray matter and then in the nucleus raphe ma gnus and/or nucleus reticularis paragigantocellularis.