The effect of self-stimulation of the lateral hypothalamus on the sleep-waking cycle in rats during alcoholization]

Directed activation of a system of positive emotional reinforcement induces regulatory effect on limbic-neocortical mechanisms of the sleep-waking cycle organization in rats after chronic alcoholization carried out in periods of decreased and increased circadian rhythms of emotional activity. In animals with high level of positive emotional drive after the alcoholization self-stimulation of the lateral hypothalamus suppresses hypersynchronous paroxysmal activity in waking EEG, decreases the content of waking in the sleep-waking cycle, restores the paradoxical phase of sleep. In animals with inhibition of positive emotional drive in consequence of alcoholization self-stimulation of the lateral hypothalamus has no essential effect on the mechanisms of regulation of the sleep-waking cycle.     

Interactions of galanin and opioids in nociceptive modulation in the arcuate nucleus of hypothalamus in rats

The fact that galanin, beta-endorphin and their receptors are present in the arcuate nucleus of hypothalamus (ARC), coupled with our previous observation that both beta-endorphin and galanin play antinociceptive roles in pain modulation in the ARC, made it of interest to study their interactions. The hindpaw withdrawal latency (HWL) in response to noxious thermal and mechanical stimulation was assessed by the hot-plate test and the Randall Selitto Test. We showed that the antinociceptive effect induced by intra-ARC injection of galanin was dose-dependently attenuated by the following intra-ARC injection of naloxone. Furthermore, intra-ARC administration of the selective mu-opioid receptor antagonist beta-funaltrexamine (beta-FNA) attenuated the increased HWL induced by intra-ARC injection of galanin in a dose-dependent manner, while the delta-opioid receptor antagonist naltrindole or the kappa-opioid receptor antagonist nor-binaltorphimine (nor-BNI) did not. Moreover, intra-ARC injection of a galanin receptor antagonist galantide attenuated intraperitoneal morphine-induced increases in HWLs. These results demonstrate that the antinociceptive effect of galanin was related to the opioid system, especially mu-opioid receptor was involved in, and that systemic morphine induced antinociception involves galanin in the ARC.     

Effects of isolation-rearing on intracranial self-stimulation reward of the lateral hypothalamus: baseline assessment and drug challenges

There is evidence that isolation rearing produces down-regulation of the dopamine D2 receptor. Therefore, isolation rearing should also modify the effects of D2 antagonists on intracranial self-stimulation (ICSS) reward. This study investigated the effect of isolation rearing on ICSS reward, and modulation of that reward by SCH23390, Raclopride and MK-801. Sprague-Dawley rats were reared alone (isolates) or in pairs from day 21 postnatal to day 75 postnatal. At this time, all rats were implanted with monopolar stimulating electrodes in the lateral hypothalamus. The ICSS rate-frequency curve-shift method was used to assess reward and operant motor function at baseline and after administration of SCH-23390 (D1 antagonist: 0.02, 0.06, 0.2 mg/kg), Raclopride (D2 antagonist: 0.01, 0.025, 0.06 mg/kg), and MK-801 (non-competitive NMDA receptor antagonist: 0.1, 0.2 mk/kg). Isolation-reared rats displayed similar measures of both basal reward and motor function when compared to socially reared controls. Isolation-reared rats were subsensitive to the reward decreasing effects of Raclopride. Socially reared rats were observed to have more variant baseline reward measures, and could be divided into distinctly different groups with different basal reward function. Isolation-rearing down-regulates D2 function but does not affect basal reward function, but some unknown factor in the social rearing environment did have a substantial effect on basal reward function.     

Descending influences from the lateral hypothalamus and amygdala converge onto medullary taste neurons

The lateral hypothalamus (LH) and the central nucleus of the amygdala (CeA) exert an influence on many aspects of ingestive behavior. These nuclei receive projections from several areas carrying gustatory and viscerosensory information, and send axons to these nuclei as well, including the nucleus of the solitary tract (NST). Gustatory responses of NST neurons are modulated by stimulation of the LH and the CeA, and by several physiological factors related to ingestive behavior. We investigated the effect of both LH and CeA stimulation on the activity of 215 taste-responsive neurons in the hamster NST. More than half of these neurons (113/215) were modulated by electrical stimulation of the LH and/or CeA; of these, 52 cells were influenced by both areas, often bilaterally. The LH influenced more neurons than the CeA (101 versus 64 cells). Contralateral stimulation of these forebrain areas was more often effective (144 responses) than ipsilateral (74). Modulatory effects were mostly excitatory (102 cells); 11 cells were inhibited, mostly by ipsilateral LH stimulation. A subset of these cells (n = 25) was examined for the effects of microinjection of DL-homocysteic acid (DLH), a glutamate receptor agonist, into the LH and/or CeA. The effects of electrical stimulation were completely mimicked by DLH, indicating that cell somata in and around the stimulating sites were responsible for these effects. Other cells (n = 25) were tested for the effects of electrical stimulation of the LH and/or CeA on the responses to taste stimulation of the tongue (32 mM sucrose, NaCl and quinine hydrochloride, and 3.2 mM citric acid). Responses to taste stimuli were enhanced by the excitatory influence of the LH and/or CeA. These data demonstrate that descending influences from the LH and CeA reach many of the same cells in the gustatory NST and can modulate their responses to taste stimulation.     

Arterial blood pressure and heart rate changes during self-stimulation by dogs in the basal forebrain region, lateral preoptic area, hypothalamus, ventral midbrain and amygdala.

In dogs pressing a lever for a brain-stimulation reward, arterial blood pressure (ABP) was elevated for 20 out of 24 sites tested, but this effect was usually conspicuous only at twice the threshold current sustaining stable performance. Hypertension was seen only in one ventral tegmental and two hypothalamic sites. In three anterior placements the ABP and heart rate (HR) increased more upon a fixed ratio than on continuous reinforcement. In most sites, self-stimulation was accompanied by cardiac acceleration; however, in some placements the HR was similar to or even less than control values. Continuous stimulation (5-10 sec) at one nucleus accumbens and four hypothalamic sites by the experimenter was aversive and produced a clearcut pressor response. The cardiovascular changes seem to depend on a spread of current to brain centres controlling circulatory functions and also, to some extent, on the animal's motor activity. The results contradict the claim that a causal relationship exists between the autonomic concomitants of self-stimulation and the intrinsic nature of the brain-stimulation reward.     

A comparison of the efficiency of stimulation of the right and left lateral hypothalamus during a self-stimulation reaction

Higher rate of the right-side self-stimulation of the lateral hypothalamus than of the left-side was found in freely behaving (30 +/- 8 versus 16 +/- 5 pressings per minute) and fixed rabbits (15 +/- 3 versus 10 +/- 2 pressings per minute, accordingly) under conditions of optimal current (current strength was leveled about the thresholds of food motivational reactions).     

Pentagastrin modulation of the neuronal sensitivity of the lateral hypothalamus to noradrenaline and dopamine

Experimental study is dedicated to mechanisms of interaction of pentagastrin and monoamines (noradrenaline and dopamine) at the level of single neurones of the rabbits lateral hypothalamus under alimentary motivation and under saturation. It is shown that pentagastrin can modulate the effects of noradrenaline and dopamine on neuronal impulse activity in hungry and fed up animals, and the character of its action depends on the rabbits initial state. It is suggested that pentagastrin is a factor initiating alimentary motivational excitation, while noradrenaline maintains the latter at the definite level up to obtaining useful result by the animal, when dopaminergic mechanisms participating in the process of reinforcement join the noradrenergic ones.     

Binding sites of opiates and endogenous opioids in the oocytes of the toad Bufo viridis

The binding of labelled naloxone, morphine and (D-Ala2,D-Leu5)enkephalin (DADL) to oocyte membranes of the toad Bufo viridis was investigated. The opiate antagonist naloxone binds to the membranes much more effectively than morphine or DADL. The binding of [3H]naloxone is reversible and saturating. The bound [3H]naloxone is readily replaced by unlabelled naloxone or bremazocine (kappa-agonist), far less effectively by morphine (mu-agonist) and SKF 10.047 (sigma-agonist) and is not practically replaced by DADL (delta-agonist), beta-endorphin (epsilon-agonist) and other neuropeptides. Analysis of experimental results in Scatchard plots revealed two types of binding sites with a high (Kd = 15 nM) and low (Kd = 10(3) nM) affinity for naloxone. The number of sites responsible for the binding of naloxone possessing a high affinity is 16 pmol-/mg of oocyte homogenate protein, i.e., 20-50 times as great as in the toad or rat brain. Trypsin and p-chloromercurybenzoate decrease the binding of [3H]naloxone. The oocyte extract is capable of replacing the membrane-bound [3H]naloxone, on the one hand, and of inhibiting the smooth muscle contracture of the rabbit vas deferens, on the other. This inhibition is reversed by naloxone and can also be induced by bremazocine, but not by morphine, DADL and SKF 10.047. In all probability oocytes contain compounds that are similar to opiate kappa-agonists. It may also be possible that these compounds mediate their effects via specific receptors and are involved in the control over maturation of oocytes and early development of toad eggs.     

Electrical activity of the lateral hypothalamus related to food-procuring movements of rats

On freely moving albino rats we demonstrated that, when fast food-procuring movements are performed, the mass electrical activity of the lateral hypothalamus (LH) is suppressed 1.6–2.0 sec before the movement beginning recorded with a photoelectrical device. Videorecording of the movements and recording of the spike activity of LH units showed that the latter are activated 1.0–0.1 sec before the movement initiation. The LH is considered a motivation-related structure, which serves as a source providing an increase in the excitability of the structures involved in the control of food-procuring movements and, further on, supporting this increased excitability. The LH is also a component of the mechanisms providing formation of the motor program. The role of the LH in the ensemble of motor centers, which organize and control voluntary movements, is discussed.     

Effect of lesions of the medial and lateral portions of the amygdala on motor activity in rats

In four groups of rats: with medial amygdala lesions, AMe, sham operated medial, AMe-C, with lateral amygdala lesions, LA, and sham operated lateral, LA-C,--motor activity was tested in small electro-magnetic cages before and after ablations. The obtained data showed an increase of motor activity only in AMe rats. Possible functional differentiation of modulatory mechanisms of the amygdala is discussed.     

Role of the lateral hypothalamus in sleep

Sleep and Biological Rhythms -     

The contribution of the amygdala and hypothalamus to the shaping of hippocampal theta activity

Under chronic experiment of 15 rabbits the hippocampal electrogram character has been studied under electrical, cholinergic, monoaminergic stimulation of the hypothalamus before and after unilateral electrocoagulation of stria terminalis. The synchronizing hypothalamic influence caused by the given stimuli on hippocampal theta-rhythm has been shown to be completely and irreversibly blocked up by the stria terminalis lesion. A leading role of the amygdala-hypothalamic interrelations in hippocampal theta activity formation is suggested.     

Impulse activity of neurons in the lateral hypothalamus during microionophoretic administration of melatonin and noradrenaline in rats

Microionophoretic administration of melatonin into the perineuronal space of lateral hypothalamic neurons in WAG and Fischer-344 rats decreased the firing rate and regularized activity of the cells. Moreover, the effects of melatonin completely blocked the activation of neurons and changes in their pulse activity produced by norepinephrine. The effects of melatonin on neuronal activity in behaviorally active stress-resistant WAG rats were more pronounced than in behaviorally passive stress-predisposed Fischer-344 rats. These data suggest that stress-protective activity of melatonin is associated with inhibition of the pulse activity of neurons in emotiogenic structures of the brain and changes in neuronal sensitivity to norepinephrine.