Dynamics of neuronal activity in the lateral preoptic area of hypothalamus in the course of sleep-waking cycle

Frequency and patterns of activity of 106 neurons in the lateral preoptic area of unanesthetized cats were studied under conditions of indolent head fixation. It was shown that this structure contains two somnogenic neuronal populations with different functions. Neurons increasing their discharge frequency during transition from active to quiet wakefulness and subsequent sleep development to the point of phasic stage of paradoxical sleep development are considered as elements of an anti-waking system, which is involved in the mechanisms of sleep onset and deepening by means of inactivation of the arousal system. Neurons displaying the highest firing rates during light slow-wave sleep and synchronization of discharges with sleep spindles are considered as elements of a slow-wave sleep network.     

The extended amygdala system and self-stimulation of the lateral hypothalamus in rats: modulation with opiates and opioids

Wistar male rats were implanted with bipolar electrodes in the lateral hypothalamus to study self-stimulation reaction in the Skinner box. Simultaneously, the microcanules were implanted into the central nucleus of the amygdala to inject the drugs studied (1 microl in volume for each injection). The blockade of CRF receptors (astressin 1 microg) or sodium influx ionic currents (xycaine, or lidocain 1 microg) by means of intrastructural administration of drugs into the amygdala descreased self-stimulation reaction of the lateral hypothalamus in rats by 29-55%. The inhibition of D2 and D2 dopamine receptors in the amygdala with SCH23390 (1 microg) or sulpiride (1 microg), respectively. reduced self-stimulation too, but in less degree. On the background of blockade of CRF (astressin) and dopamine (sulpiride) receptors, as well as sodium influx ionic currents (lidocain) in the amygdala neurons, psychomotor stimulant amphetamine (1 mg/kg) and barbiturate sodium ethaminal (5 mg/kg) supported their psychoactivating effect on self-stimulation (+30-37%), but fentanyl (0.1 mg/kg) had got no effect. Fentanyl activated self-stimulation moderately only after blockade D1 dopamine receptors with SCH23390. After blockade of CRF receptors, leu-enkephaline strengthened its depressant effect on self-stimulation reaction (-89%). Therefore, if the modulating influence of the amygdala on the hypothalamus is diminished, the reinforcing effects of opiated (fentanyl) and opioids (leuencephaline) will block, but there will be no effect for psychomotor stimulant amphetamine and barbiturate sodium ethaminal.     

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).     

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%.     

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.     

The effect of acute alcoholization on the neuronal activity of the normal ventromedial hypothalamus and in pharmacological actions on the brain monoaminergic and opiate systems]

In experiments on white outbred male rats the specificity was studied of the influence and mechanisms of action of acute alcoholization (30%-solution of ethanol, intraperitoneally, 0.7 g/kg) on the activity of functionally different neurones of the ventromedial hypothalamus. Experimental results showed that the neurones, the activity of which lowered after saturation (I-st type), increased the discharges frequency at administration of ethanol. Nerve cells, the activity of which increased (II-nd type) and did not change (III-nd type) after saturation, had inhibitory character of reaction in response to alcoholization. The increase of serotonin content in the brain elicited by intraperitoneal administration of 5-OTPh (50 mg/kg) blockaded the action of ethanol on the nerve cells of the I-st type and did not change the effect of the alcohol on the neurones of the II-nd and III-nd types. Preliminary lowering of the noradrenaline level in the brain (disulphiram, intraperitoneally, 100 mg/kg) and blockade of opiate receptors (nalorphine, 5 mg/kg) fully eliminated ethanol influence on the activity of all types of neurones.     

The effect of alcoholization on the behavioral reactions of rats in an 8-arm radial maze

The influence of 20% alcohol consumption on training of low-active rats in 8-arm radial maze was studied. One group of animals was trained before and the other group after the alcoholization. All the animals acquired the conditioned reaction in the radial maze. However, the behavioral difference between the groups consisted in spatially-motor asymmetry. The rats trained before the alcohol consumption had less stereotyped behavior and more distinctly preferred to enter the maze arms at the angle of 45 degrees than the animals trained after the alcohol consumption. After the alcohol consumption, rats more frequently refused from behavioral task performance in comparison with the animals trained after the alcoholization. The influence of alcohol consumption of learning and memory in low-active rats is discussed.     

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.     

Hypothalamic self-stimulation during the abstinence syndrome in morphine-dependent rats

Rats with lateral hypothalamic self-stimulation were treated chronically with morphine (30 injections in the course of 15 days) in doses increasing stepwise from 20 to 120 mg/kg per injection. Morphine facilitated self-stimulation from the 9th injection. Both short-term abstinence (16-18 hours) and cessation of the narcotic resulted in inhibition of the response. Full suppression of self-stimulation occurred under the administration of nalorphine, morphine antagonist, in a dose of 5 mg/kg.     

The effect of neurotropic substances on the self-stimulation reaction at the thalamic level]

The effect of d-amphetamine, cocaine, caffeine, morphine, imipramine, phenobarbital, LSD-25, benactyzine, meprobamate, diazepam, chloridiazepoxide on the lateral hypothalamic self-stimulation of rats was investigated. D-amphetamine, cocaine, caffeine, morphine, imipramine decreased the threshold of selfstimulation. Meprobamate, diazepam, chlordiazepoxide failed to influence this index, but increase the intensity of self-stimulation during the threshold, the optimum and more than the optimum cirrent intensity. Benactyzine, LSD-25, phenobarbital decreased the threshold and increased the frequency of self-stimulation during all the current intensities. A comparative study of the above results showed the agents of the first group to exert a direct stimulating action on the positive reinforcement system. Tranquillizers activated this system due to their depressive action on the negative reinforcement system. Benactyzine, LSD-25, phenobarbital activated the system and depressed the system of negative reinforcement.     

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.     

Naloxone blocks the excitatory effect of ethanol and chlordiazepoxide on lateral hypothalamic self-stimulation behavior

Ethanol (ETOH, 0.5 g/kg) and chlordiazepoxide (CDP, 4.0 mg/kg) enhance operant responding by rats for lateral hypothalamic (LH) self-stimulation (SS). Naloxone (NOX, 5.0 mg/kg) does not affect LH SS or blood alcohol level, but prevents the increased responding for LH SS produced by ETOH and CDP. Thus, ETOH and CDP, but not brain stimulation reward itself, may release an endogenous opioid whose action at opiate receptors results in an excitatory behavioral (euphorigenic?) effect which can be blocked by NOX.