Hypothalamo-limbic involvement in modulation of tooth-pump stimulation evoked nociceptive response in rats.

The hypothalamo-limbic system has been implicated in recognizing the affective significance of pain and elicitation of related emotional responses. Several evidences from different studies support a role of these areas in endogenous analgesic mechanisms for pain modulation as elucidated by different pain tests in more than one animal model. In the above context, the aim of this study was to investigate the relative effectiveness of the pain modulatory action of hypothalamic and limbic structures in rat using similar stimulation parameters, and studying the effect on tooth pulp stimulation evoked jaw opening reflex (TP-JOR). To achieve the objective, unilateral stimulation of hypothalamic (lateral = LH; ventromedial = VMN; anterior = AH) and limbic areas (amygdala = AMYG; hippocampus = HIPP) was done on the TP-JOR test. A significant reduction in the amplitude of EMG recorded from the digastric muscle (dEMG) as a result of tooth-pulp stimulation was observed on stimulation of LH, VMN, AMYG and HIPP but not from AH. Also, the magnitude of this effect was almost similar from these areas. The results suggest that these areas (except AH) have an antinociceptive role in tooth-pulp stimulation evoked pain response.

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.

Plasticity of hippocampal and motor cortical pyramidal neurons induced by self-stimulation experience.

The self-stimulation (SS) induced neuronal plasticity was observed in CA3 hippocampal and layer V motor cortical pyramidal neurons. SS experience was allowed daily for a total of 1 hour for 10 days through four bipolar electrodes implanted bilaterally in lateral hypothalamus (LH) and substantia nigra-ventral tegmental area (SN-VTA) in adult male Wistar rats. Examination of pyramidal neurons stained by rapid Golgi technique was made in a total of 1,600 neurons out of 80 rats consisting of 4 groups. The dendritic intersections were quantified upto 200 and 120 microns radial distances in apical and basal dendrites respectively. The CA3 hippocampal and layer V motor cortical pyramidal neurons of SS group revealed significant increase (P < 0.001, two-way ANOVA) in dendritic intersections in both apical and basal dendrites, compared to normal control (NC), sham control (SH) and experimenter-administered (EA) group of animals. These results demonstrate that SS experience promotes increase in dendritic length in hippocampal and motor cortical pyramidal neurons.

Renal water handling evaluated by lithium clearance following adrenergic and cholinergic stimulation of the lateral hypothalamic area

Male Wistar rats weighing 230-3--g were used to characterize the participation of adrenerg and cholinergic receptors of the lateral hypothalamic area (LHA) in the control of renal water excretion. Since stimulation of adrenergic or cholinergic receptors has no effect on glomerular filtration rate, the antidiuresis and significant delay in urinary flow observed after lateral hypothalamic stimulation with carbachol (CCh) (0.036 ñ 0.005 to o.019 ñ 0.003 µlmin-1 100g body weight-1) and noradrenaline (Nad) (0.024 ñ 0.005 to 0.025 ñ 0.004 µl min-1 100g body weight-1) are secondary to an increase in distal tubular fluid reabsorption (DFR). Data are reported as means ñ SEM for ten rats each group. Tubular water measured by lithim clearance demonstrated that LHA stimulation with CCh (2.8 nmol in 1 µl) and Nad (30.0 nmol in µl) leads to a significant reduction in proximal water reabsorption with CCh, 93.3 ñ 2.6 to 85.4 ñ 1.4%; Nad, 92.7 ñ0.9 to 88.6 ñ 1.3%), with a simultaneous and significant incrase in fluid reabsorption along the post-proximal nephrom segments when compared to control (CNa) (CCh, 6.7 ñ 0.7 to 14.5 ñ 1.1%; Nad 8.2 ñ 0.8 to 11.4 ñ 1.6%) These effects are blocked by muscarinic (atropine, 5 nmol in 1 µl) and alpha-1 adrenoceptors (prazosin, 4 nmol in 1 µl) antagonists. The results indicate the effective participation of the post-proximal nephron in the antidiuresis occurring after cholinergic and adrenergic LHA stimulation

The effect of phentolamine on the pressor reponse to centrallly administered clonidine in rats

In the present study we investigae the effect of the previous injection of phentolamine (anonspecific alfa-adrenergic antagonist) into the lateral hypothalamus (LH) and lateral ventricle (LV) on the pressor and bradycardic responses produced by the injection of clonidine (an alfa-2 adrenergic agonist) into these same areas of conscious rats. The injections of clonidine into the LH produced pressor (39 ñ 5 and 38 ñ 3 mmHg, respectively) and bradycardic responses (-65 ñ 16 and -94 ñ 13 bpm, respectively). Previous injections of phentalamine into the LH or LV reduced the pressor response to clonidine injected into the same areas (DeltaMAP = 13 ñ 6 mmHg for LH and 1 ñ 3 mmHg for LV). No reduction was observed when clonidine was injected into the LV after the injection of phentalamine into the LH. No changes in bradycardic responses were observed after treatment with phentolamine. The present results show the participation of alfa-adrenergic receptors in the pressor response to centrally administered clonidine but not in the bradycardic reponse. The data also suggest that the pressor effect by the injection of clonidine into the LH is due to the activation of alfa-adrenergic receptors located specifically in this area. The pressor response after injection of clonidine into the LV and of phentolamine into the LH is due to the action of clonidine on other cerebral areas

Inhibition of renal electrolyte excretion by gabaergic pathways of the lateral hypothalamic area

Injection of gamma butyric acid (GABA) into the lateral hypothalamic area of unrestrained conscious rats caused a decrease in renal electrolyte excretion with an increase in urinary flow. When picrotoxin, a specific inhibito of gabaergic pathways, was administered, a significant increase in renal water and electrolyte excretion occured. The effect of simultaneous injection of pidrotoxin and GABA into the same site indicate that picrotoxin was less potent in reversing tyhe effect induceb by GABA than GABA was in reversing the effect of picrotoxin. We conclude that GABA acts directly on the neuronal mechanisms involved in the control of water and elecltrolyte excretion, perhaps by exerting a tonic inhibitory action on renal electrolyte excretion

Participation of opiate pathways in the lateral hypothalamic area in the control of renal electrolyte and water excretion

Injection of Met-enkephalin (0.05, 0.25 and 0.50 µg in 1 µl) solutions into the lateral hypothalamic area (LHA), of unrestrained and unanesthetized rats caused a significant decrease of sodium (0.30 ñ 0.13 to 0.07 ñ 0.01, P < 0.05) and potassium (0.61 ñ 0.17 to 0.21 ñ 0.04, P < 0.05) excretion. When the blocking agent nalaxone (0.20 µg in 1 µl) was injected alone, a signifricant increase of sodium (0.34 ñ 0.04 to 0.96 ñ 0.28, P < 0.05) and potassium (0.76 ñ 0.13 to 1.72 ñ 0.30, P < 0.05) excretion was observed. However, a dose-response relationship was not observed. However, when in another experiment naloxone was injected before Met-enkepalin into the same area, reversal of the effect of naloxone occured, with decreased sodium and potassium excretion. We conclude that the enkephalinergic pathway of the LHA when stimulated with Met-enkephalin plays an inhibitory role in the contorl of sodium and potassium excretion