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 mug/0.5 mul) or electrical stimulation depresses the tail withdrawal reflex to noxious heating of the skin were examined. Among other hypothalamic sites found to be sensitive to morphine or to an electrical stimulus, the posterior part of the lateral hypothalamic area (LHA) was the only portion of the hypothalamus that was strongly sensitive to both manipulations. A 15-sec period of 35-muA sine-wave stimulation of the LHA significantly increased the latency of the tail reflex for periods up to 30 min. The effects of intraperitoneal administration of antagonists to opioids (naloxone), 5-hydroxytryptamine (methysergide), noradrenaline (phenoxybenzarnine), dopamine (haloperidol and acetylcholine (atropine and mecamylamine) on the antinociceptive effects of LHA stimulation were also examined. Naloxone, methysergide, and atropine (all given at doses of 0.5 and 1.0 mg/kg attenuated the effects of LHA stimulation in a dose-dependent manner. Phenoxybenzamine, but not haloperidol (both at the dose of 1.0 mg/kg), was also effective but dose-dependent curves could not be constructed. Mecamylamine (1.0 mg/kg) reduced the duration but no the peak effect of stimulating the LHA. We conclude that antagonism at the level of opioid, serotonergic, adrenergic, and muscarinic cholinergic receptors, but not dopamine or nicotinic 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 mesencephalic periaqueductal gray matter and then in the nucleus raphe magnus and/or nucleus reticularis paragigantocellularis.

Effect of lesions of areas of brain--stimulation reward of one region of brain on operant behaviour for receiving electrical stimulation into sites of another region and on operant behaviour for food reward.

It was aimed to study the effects of lesions of a self-stimulation (SS) area of one region of brain on the SS of another region, and on feeding behaviour in adult Wistar rats (males). The two regions proposed for study were the lateral hypothalamus (LH) and the substantia nigra-ventral tegmental area (SN-VTA). The objective was to elucidate whether each region had its own neural organization for SS behaviour or not, and whether the neural substrates of SS behaviour and feeding behaviour were one, or separate. Four bipolar electrodes were implanted bilaterally in LH and SN-VTA in each rat, and their SS pedal press rates for rewarding electrical stimulations were characterised. The rats were also trained in operant conditioning paradigm for receiving reward of food grains in FR-30 schedule. Their free-field food intake in home cages was measured. Later, electrolytic lesions of the four electrode sites were made one after another at 2-day intervals through the same biopolar electrodes. After each lesioning, the SS of the same and of the other electrode sites, and the operant performance of FR-30 food reward schedule, and daily free-field food intake (in home cage) were determined. Lesions of the LH SS site always disrupted SS-of contralateral LH but not of SN-VTA SS. Lesions of SN-VTA had not modified contralateral SN-VTA SS. A study of effects of ipsilateral lesions of LH SS site on SN-VTA SS, or of lesions of SN-VTA SS site on LH SS, revealed a range of changes, as were also effects on the FR-30 operant performance and daily food intake. Medium size lesions of SS area made in one region affected the SS of that area but not usually the SS of the other region. Large lesions of one region affected the SS of the other regions also. With large lesions, feeding behaviour also was affected, firstly of the operant type and secondly the free-field type.