The effect of different activating influences on the self stimulation reaction]

A study was made of the influence on self-stimulation of non-painful sensory stimuli of different modalities, and of intra-brain stimulations of emotionally positive and neutral points with the wiew to elucidate the specificity of certain functional relations appearing during interaction between emotionally negative and positive conditions. The data obtained attest that the influence of various excitation sites on self-stimulation reactions depends not so much on the strength of the stimuli, as on the specific neurophysiological organization of emotionally negative zones in the brain. A reciprocal enhancement of excitation of self-stimulation zones points to a certain non-specificity of positively reinforced structures.     

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.     

The influence of damage to the septum pellucidum on the effects of electrical stimulation of the hypothalamus in rabbits]

In chronic experiments the influences of septal lesions on the behavioural emotional effects of electrical stimulation of various hypothalamic nuclei were investigated. The total ablation of the septum caused irreversible increase of the lateral hypothalamus self-stimulation and reversal of the negative emotional responses (escape--avoidance) to the medial hypothalamus stimulation into the positive self-stimulation behaviour. When the septal ablation was only partial, involving mainly the medial nucleus, effects were weaker and lasted only 2-3 days after the surgery. The role of the septum in the septohippocampal behavioural inhibition system (J. Gray) is discussed.     

Effect of stimulation of "emotiogenic" brain structures on pyramidal tract responses

In experiments with stimulation of emotiogenic zones (lateral and medial hypothalamus, raphe nuclei), as a conditioning agent, a study was made of summary responses of the pyramidal tract to electrical stimulation of the sensorimotor cortex in immobilized and freely moving rats. The responses exhibited a positive early direct P-component (mean latency 0.8 +/- 0.3 ms) and a late synaptic N-component (mean latency 1.8 +/- 0.5). Reduction of the N-component amplitude was observed during stimulation of the lateral hypothalamus, and its enhancement during stimulation of the medial hypothalamus. Stimulation of the raphe nuclei produced variable, statistically non-significant changes. The experiments have shown that the identified pyramidal neurones tend to reciprocal reactions during stimulation of positive and negative emotiogenic structures. Inhibitory and excitatory influences of the respectively positive and negative emotiogenic structures on pyramidal neurones are due to indirect modulating actions on presynaptic structures.     

Participation of GABA- and dopaminergic mechanisms of the bed nucleus of stria terminalis in reinforcing effects of psychotropic drugs mediated via the lateral hypothalamus

The purpose of the investigation was to elucidate significance of GABA and dopamine systems of the bed nucleus of stria terminalis for the reinforcing effects of a number of psychotropic drugs (opiates, opioids, psychostimulants) on self-stimulation of the lateral hypothalamus in rats. To the Wistar male rats, bipolar electrodes were implanted in the lateral hypothalamus to study self-stimulation reaction in the Skinner box. Simultaneously, the microcannules were implanted into the bed nucleus of stria terminalis to inject the drugs under study. Some drugs, xycaine, or lidocain, a blocker of sodium influx ionic currents, antagonists of GABAA receptors bicuculline, D1 dopamine receptors SCH23390 and D2 dopamine receptors sulpiride which were administered intrastructurally into the bed nucleus of stria terminalis, were used for pharmacological analysis. Xycaine > SCH23390 = bicuculline inhibited self-stimulation of the lateral hypothalamus. The reinforcing properties of a number of psychoactive drugs (amphetamine, Fentanyl, sodium ethaminal and leuenkephaline) were changed on the background of their action. It is concluded that the bed nucleus of stria terminalis controls the hypothalamic self-stimulation via GABA- and dopaminergic mechanisms. GABA realizes the negative (inhibitory) action. The direct positive (activating) effect on the lateral hypothalamus is realized through D1 dopamine receptors, and D2 dopamine receptors of the bed nucleus of stria terminalis limit the positive effects of narcogenic drugs.     

Effect of diazepam, meprobamate and amizyl on the emotional reactions of the rabbit to hypothalamic stimulation

The influence of minor tranquilizers (diazepam, meprobamate and beuactizine) on the hypothalamically elicited emotional responses was studied in chronic experiments on rabbits. The positive self-stimulation elicited from the lateral hypothalamus was facilitated by all used tranquilizers. On the first day of administration of the drugs the rate of self-stimulation increased markedly. The rate of self-stimulation was still mildly enhanced on the second day and returned to its initial value on the third day. The avoidance behaviour elicited from the medial hypothalamus changed to obvious self-stimulation after the administration of diazepam and meprobamate. The reversed behaviour preserved on the second day, while on the third day the animals resumed their avoidance behaviour. It was depressed by benactizine injection and some activation of exploratory behaviour was observed.     

Relation between the dynamics of the extinction process and the initial rate of hypothalamic self-stimulation in the rabbit

In experiments on rabbits with electrodes chronically implanted in the lateral hypothalamus, dynamics was studied of extinction of self-stimulation reaction as a result of cancellation of intracerebral reinforcement. General dynamics of extinction of the unreinforced instrumental actions and behavioural manifestations of orienting-investigating reaction were revealed. It was found, that in 30% of rabbits, the orienting reaction appearing as a result of "discordance" between expected and actual afferentation is attended by a species-specific form of behaviour, expressed in the form of hind paws synergic strokes against the floor. It is suggested that these strokes may be a somatic expression of a negative emotional state of animals during self-stimulation extinction. The comparison of extinction dynamics with the level of self-stimulation background frequency showed a relative independence of the strength of drive towards getting positive emotions on motivational effects created by electric stimulation of the reinforcing brain structures.     

Interhemispheric asymmetry of positive emotional reactions in rats

Interhemispheric asymmetry of positive emotional reactions was studied in rats: satisfaction of drinking need and self-stimulation. Successive inactivation of the hemispheres was carried out by potassium spreading depression. Switching off of the right as well as the left hemispheres symmetrically influenced the whole quantity of the water, drunk by the rats to a full thirst satisfaction, i. e. the magnitude of need. However, at different stages of drinking need satisfaction an interhemispheric asymmetry was observed: under a strong drinking motivation the right hemisphere dominated, under a weak motivation--the left one. Switching off of the right hemisphere lowered the frequency of self-stimulation of the lateral hypothalamus and switching off the left one heightened it, testifying to the dominance of the right hemisphere in the reaction of self-stimulation. This reaction was also characterized by asymmetry of the lateral hypothalamus nuclei; reactivity to hemispheres inactivation (decreasing or increasing of self-stimulation frequency) of the right nucleus was more expressed than that of the left one.     

Shift of the catecholamine levels at stimulation of the hypothalamic emotiogenic zones

Using models of electrical self-stimulation of the positive emotiogenic zones and stimulation of the negative emotiogenic zones of the hypothalamus in rats, we demonstrated that both these stimulations increase the noradrenaline level in the frontal cortex. This shows a nonspecific nature of activation of the dorsal noradrenergic bundle, resulting from motivational excitation. When the frequency of self-stimulation reaction remained stable, activation of the dorsal noradrenergic bundle was moderate, and at decay of the above reaction it returned to the control level. Behavior connected with activation of the motor functions was characterized by an increase in the dopamine and noradrenaline levels in the caudate nucleus. In theglobus pallidum, the dopamine content changed only under conditions of stimulation of the negative emotiogenic zones: these were an increase in the reaction of active avoidance and a decrease in passive avoidance.     

Emotional manifestations in the electrical stimulation of the hypothalamic nuclei in adult and old rats

In experiments on adult (9-10 months) and old (24-26 months) white Wistar rats behavioural manifestations under electrical stimulation of the ventromedial hypothalamus nucleus and self-stimulation (SS) of the lateral hypothalamic region were studied. It has been found that with age electrical thresholds of negative emotional manifestations decrease with invariable SS thresholds. In old rats, in comparison with the adult ones, SS frequency is lower, maximum SS proceeds at lower currents, the range of currents capable to evoke an intensive SS is narrower, SS motivational component is less expressed. The obtained data testify that in old rats there exist neurophysiological preconditions for prevailing of negative emotional manifestations.     

Effect of the "memory peptide" ACTH 5-10 on the self-stimulation reaction of rabbits

Experiments on rabbits were made to study variation in the frequency of the self-stimulation reaction from the lateral hypothalamus under the effect of the corticotropin fragment ACTH5-10. Intraperitoneal administration of the peptide in a dose of 50 micrograms/kg that causes the improved training in different behavioral models produces no significant effect on the mechanism of intracranial positive reinforcement. Intraventricular injection of 5 microliters of 0.9% NaCl leads to a short-term suppression of the self-stimulation reaction. Administration of 50 pcM/kg ACTH5-10 in the same volume of physiological saline completely abolishes the inhibitory action of the intraventricular injection itself.     

Behavioral reactions to stimulation of the emotiogenic zones of the brain in the rats with different individual experience

Emotional reactions evoked by electric stimulation of the hypothalamus and amygdala were studied in white outbred rats, grown either in conditions of isolation or in community. The method of self-stimulation in shuttle box was used. The values of self-stimulation reaction were significantly lower and those of avoidance reactions were higher in animals bred in isolation. Their food-procuring behaviour disappeared faster at stimulation of the negative emotiogenic zones. The observed differences are due to plastic reorganization of the brain reinforcing systems.     

Conditioned-reflex activation of electrical self-stimulation of the brain: a model of a situational craving for narcotics]

Rats with electrodes implanted into lateral hypothalamus were trained to press a lever to obtain electrical stimulation of the brain. After elaboration of self-stimulation (SS) conditioning of morphine-induced activation of SS-response was carried out. Five pairings were performed of morphine (3 mg/kg, i.p.) administration and SS in the box with distinct environmental cues (brightness, color, floor texture, background noise). After morphine withdrawal activation of SS was reproduced after simple placing of the animal in "conditioned" chamber. This effect was naloxone-sensitive. The observed effect is considered to be the adequate model of addictive substances craving.     

Neuronal activity in self-stimulation zones of the hypothalamus in motivational and emotional states induced by electrical and natural stimuli

Study of neuronal activity in hypothalamus areas of self-stimulation in rats showed two types of neurones. Some of them had an increased frequency at food and water deprivation and they had maximum activation at current stimulation, eliciting motivational behaviour. Others had maximum activation at current level, eliciting self-stimulation effects, some of these neurones had positive activating relation to satisfaction of food requirements. The obtained data are considered as morphofunctional substrate of motivational and emotional states.     

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.     

Apparent independence of opiate reinforcement and electrical self-stimulation systems in rat brain.

Only very high doses of naloxone (≥40 mg/kg) were effective in attenuating intracranial self-stimulation elicited from the caudate nucleus and lateral hypothalamus. Naloxone did not differentially effect self-stimulation in the two brain areas. The results provide no evidence for an important role of the endogenous opioid-opiate receptor mechanism in self-stimulation, and suggest an independence of the opiate reinforcement and electrical self-stimulation systems in the rat brain.     

Mechanism of the analgesic effect of narcotic analgetics]

A study was made of the effect of morphine, promedol, phentanyl, pentazacine and psychostimulant d,l-amphetamine on the threshold of pain sensitivity and self-stimulation of the hypothalamus and the septum in rats. Electrical stimulation of the systems of positive reinforcement of the hypothalamus and the septum, and also analgetics increased the threshold of pain sensitivity, whereas d,l-amphetamine failed to influence it. D,l-amphetamine and morphine facilitated, promedol failed to influence, phentanyl decreased and pentazacine completely depressed the hypothalamic self-stimulation. The septal self-stimulation remained unaltered under the effect of morphine, promedol, phentanyl, but was decreased under the effect of pentazacine and increased against the background of d,l-amphetamine. A conclusion was drawn that the analgetic action and that activating the positive emotion were independent effects of the psychotropic agents.     

Functional asymmetry of the frontal cortex and lateral hypothalamus of cats during food instrumental conditioning

The synchronism and latency of auditory evoked potentials (EP) recorded in symmetric points of the frontal cortex and lateral hypothalamus of cats were measured at different stages of instrumental food conditioning and after the urgent transition to 30% reinforcement. Correlation coefficients between EPs in the cortex and hypothalamus were high (with left-side dominance) at the beginning of the experiments, when food motivation was high, and during the whole experiments in cases of high-probability of conditioned performance. Analysis of early positive P55-80 EP component showed that at all conditioning stages the peak latency of this component was shorter in the left cortical areas than in symmetrical points, whereas in the hypothalamus the shorter latency at the left side was observed at the stage of unstable conditioned reflex, and at the stage of stable reflex the latency of the studied component was shorter at the right side. During transition to 30% reinforcement, the latency was also shorter in the right hypothalamus. It is suggested that the high left-side correlation between the hypothalamus and cortex was associated with motivational and motor component of behavior rather than reflected the emotional stress induced by transition to another stereotype of food reinforcement (30%).     

Effect of chronic stimulation of the emotionogenic zones of the hypothalamus on the status of carbohydrate metabolism in the rabbit

In chronic experiments on rabbits receiving for 3 months low doses of cholesterol (60 mg per 1 kg of body weight daily), a repeated prolonged (2 h daily) intermittent stimulation of negative and positive emotive zones of the hypothalamus through implanted electrodes (eliciting avoidance and self-stimulation reactions correspondingly),--resulted in uniform disturbances of carbohydrate metabolism. There was a significant reduction of glucose tolerance in comparison with the control group of rabbits with implanted electrodes, as well as a gradual development of a slight, but stable neurogenic hyperglycemia. Simultaneously, in both experimental rabbits groups there were an equal increase of alimentary hypercholesterolemia and a development of persistent neurogenic arterial hypertension.