The effect of adrenoblockers on the neurons of the lateral hypothalamus under the action of pentagastrin]

To test the hypothesis of interaction pentagastrin (PG) noradrenaline (NA) in central neurochemical mechanisms of food motivation, we studied the activity of single neurons in lateral hypothalamus (LH) after s.c. PG injection. Following PG injection microiontophoresis (MIF) of propranolol prazosin was made. PG-induced changes were similar to neuronal activity in rabbits LH after 24-hour food deprivation in 59%. Propranolol-induced changes were following firing pattern in the process of food uptake in 68%. Prazosin MIF induced firing pattern of neuronal activity of saturated rabbits in 60%.     

Effects of electrical stimulation of ventral septal area on firing rates of pyrogen-treated thermosensitive neurons in preoptic anterior hypothalamus from rabbits

Although there is considerable evidence supporting that fever evolved as a host defense response, it is important that the rise in body temperature would not be too high. Many endogenous cryogens or antipyretics that limit the rise in body temperature have been identified. Endogenous antipyretics attenuate fever by influencing the thermoregulatory neurons in the preoptic anterior hypothalamus (POAH) and in adjacent septal areas including ventral septal area (VSA). Our previous study showed that intracerebroventricular (I.C.V.) injection of interleukin-1beta (IL-1beta) affected electrophysiological activities of thermosensitive neurons in VSA regions, and electrical stimulation of POAH reversed the effect of IL-1beta. To further investigate the functional electrophysiological connection between POAH and VSA and its mechanisms in thermoregulation, the firing rates of thermosensitive neurons in POAH of forty-seven unit discharge were recorded by using extracellular microelectrode technique in New Zealand white rabbits. Our results show that the firing rates of the warm-sensitive neurons decreased significantly and those of the cold-sensitive neurons increased in POAH when the pyrogen (IL-1beta) was injected I.C.V. The effects of IL-1beta on firing rates in thermosensitive neurons of POAH were reversed by electrical stimulation of VSA. An arginine vasopressin (AVP) V1 antagonist abolished the regulatory effects of VSA on the firing rates in thermosensitive neurons of POAH evoked by IL-1beta. However, an AVP V2 antagonist had no effects. These data indicated that VSA regulates the activities of the thermosensitive neurons of POAH through AVP V1 but not AVP V2 receptor.     

Effect of leukocyte pyrogen on the phagocytic properties of macrophages in tissue culture]

The effect of rabbit leukocytic pyrogen (LP) on the phagocytic activity of the peritoneal macrophages of albino mice against shigellae was investigated. The dose-effect dependence was revealed: high LP doses depressed the phagocytosis, and low ones were insufficiently effective; addition of average LP doses against the kanamycin background stimulated both the absorption phase and that of shigella digestion. Phagocytosis stimulation with LP was also accompanied by an increase of the acid phosphatase lysosomal enzyme activity in macrophages; the RNA content was not changed.     

Mechanisms of leukocyte activation during formation of leukocyte pyrogen

The inhibotors of protein synthesis--actinomycin D and cycloheximide--inhibit endogenous pyrogen production by blood granulocytes in response to stimulation by the bacterial lipopolysaccharide and specific antigranulocytic serum and have no effect on the pyrogen release by exudate leukocytes. These results indicate that the mentioned inhibitors suppress the activation phase, but not the pyrogen labilization process.     

Effect of different leukocyte pyrogen fractions on hemopoiesis

Fractionation of leukocyte pyrogen on a column of Sephadex G-75 made it possible to obtain separately the fraction stimulating the hemopoiesis and the fraction possessing the pyrogenic activity and inhibiting the hemopoiesis. Judging by the elution profile of Sephadex column G-75, substances of high molecular weight produced a stimulating action, and of low molecular weight--pyrogenic and inhibitory action. Possibly pyrogenic and inhibitory activities are connected with different substances. The nature of the inhibitory factor requires further investigation. It may be supposed that it is a substance of chalone type.     

Influence of NO on the background activity and corticofugal responses of anterior hypothalamus neurons

In acute experiments on cats we studied the modulating influence of an NO donor, nitroglycerin (NG), and a blocker of NO synthase nitro-L-arginine, methyl esther (L-NAME), on the neuronal responses in the anterior hypothalamus evoked by stimulation of evolutionary heterogeneous cortical zones. Intracerebroventricular injections of NG and L-NAME relatively rarely resulted in fundamental changes in the types of cortically evoked responses (8.8%; 65 cases among 736 testings). Yet, 72% of the L-NAME injections evoked significant increases in the frequency of the neuronal background activity, while 64% of NG injections resulted in suppression of the background activit. Possible mechanisms of modifications of the synaptic efficiency in cortico-hypothalamic projections determined by shifts in the NO concentration are discussed.     

Glucose-sensing neurons of the hypothalamus

Specialized subgroups of hypothalamic neurons exhibit specific excitatory or inhibitory electrical responses to changes in extracellular levels of glucose. Glucose-excited neurons were traditionally assumed to employ a 'beta-cell' glucose-sensing strategy, where glucose elevates cytosolic ATP, which closes KATP channels containing Kir6.2 subunits, causing depolarization and increased excitability. Recent findings indicate that although elements of this canonical model are functional in some hypothalamic cells, this pathway is not universally essential for excitation of glucose-sensing neurons by glucose. Thus glucose-induced excitation of arcuate nucleus neurons was recently reported in mice lacking Kir6.2, and no significant increases in cytosolic ATP levels could be detected in hypothalamic neurons after changes in extracellular glucose. Possible alternative glucose-sensing strategies include electrogenic glucose entry, glucose-induced release of glial lactate, and extracellular glucose receptors. Glucose-induced electrical inhibition is much less understood than excitation, and has been proposed to involve reduction in the depolarizing activity of the Na+/K+ pump, or activation of a hyperpolarizing Cl- current. Investigations of neurotransmitter identities of glucose-sensing neurons are beginning to provide detailed information about their physiological roles. In the mouse lateral hypothalamus, orexin/hypocretin neurons (which promote wakefulness, locomotor activity and foraging) are glucose-inhibited, whereas melanin-concentrating hormone neurons (which promote sleep and energy conservation) are glucose-excited. In the hypothalamic arcuate nucleus, excitatory actions of glucose on anorexigenic POMC neurons in mice have been reported, while the appetite-promoting NPY neurons may be directly inhibited by glucose. These results stress the fundamental importance of hypothalamic glucose-sensing neurons in orchestrating sleep-wake cycles, energy expenditure and feeding behaviour.     

The effect of ablation of the caudate nucleus on the alimentary zone of the lateral hypothalamus]

A conditioned food-procuring reaction previously elaborated to an acoustic stimulus was reproduced in chronic experiments on six cats by means of direct electrical stimulation of the posterior parts of the lateral hypothalamus. Folloiwng extensive bilateral electrolytic ablation of the caudate nucleus, conditioned food-procuring reaction to the stimulation of the hypothalamus could not be reproduced for 40 to 70 days. The conditioned foor-procuring reflex to the acoustic stimulus disappeared for 14 to 30 days to be subsequently spontaneously restored. After caudatotomy, a diminution of the average amplitude of background oscillations and of evoked potentials to acoustic stimuli was recorced in the examined zones of the lateral hypothalamus. The part played by the caudate nucleus in the processes of alimentary behaviour activation is discussed.     

CRF-containing neurons of the rat hypothalamus

Summary The immunoreactive CRF-neurons of the rat hypothalamus have been examined immunohistochemically employing anti-rat CRF serum. These neurons are confined to the paraventricular nucleus, dorsomedial-lateral hypothalamic area, and suprachiasmatic nucleus, and are, respectively, also immunoreactive to anti-Met-enk, -alpha-MSH, and -VIP sera. Intraventricular administration of colchicine (50 g/5 l/rat) induces a dramatic enhancement of the immunostainability of the cell somata, and also accelerates the development of immunoreactivity of other stored peptides, especially in the paraventricular nucleus.The CRF-neurons respond to adrenalectomy by showing increased immunoreactivity and an increase in the number of cell bodies; in the dorsomedial-lateral area and suprachiasmatic nucleus, there is also an enhanced immunoreactivity for alpha-MSH and VIP, respectively. CRF-cells in the paraventricular nucleus become markedly hypertrophied, but do not show any enhanced immunoreactivity for Met-enk. Since the axons of the paraventricular neurons run to the median eminence, it is probable that they are involved with the endocrine control of hypophysial ACTH release. It is concluded that the CRF-containing neurons in rat hypothalamus consist of three types which are functionally and morphologically different.     

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.