Role of the substantia nigra in the behavioural-cardiovascular integration in the cat

Electrical stimulation of the substantia nigra elicited complex patterns of response composed of somatomotor and circulatory changes. Increase in blood pressure associated with acceleration in heart rate was consistently produced by substantia nigra stimulation both in conscious and in anaesthetized cats. The respiration was either accelerated or arrested by the stimulation. Also self-stimulation of the substantia nigra elicited pressor responses. Electrical stimulation of the nucleus of the tractus solitarius paired with self-stimulation of the substantia nigra, produced regular changes in the lever-pressing rate for self-stimulation. It is suggested that the substantia nigra is probably involved in the neural mechanisms coupling the circulatory changes with the somatomotor responses.     

Interrelations of the emotionally positive and negative areas of the brain in the edible snail

Fine wire electrodes were surgically implanted in two regions of a snail's brain (Helix aspersa). To receive electrical stimulation of the brain, the tethered snail was required to displace the end of a rod. Self-stimulation delivered to the parietal ganglion resulted in nonrepetition of the operant response, whereas self-stimulation delivered to the mesocerebrum resulted in an increase in response frequency. In neurophysiological experiments it was found that extracellular stimulation of mesocerebrum inhibits spontaneous activity of serotonergic cells modulating avoidance reactions, and decreases synaptic input of a command cell for avoidance behaviour. These findings make possible intracellular investigations of the mechanisms of positive and negative reinforcement.     

Effect of the melanostatin analogue alaptide on dopamine-dependent behavior in rats reared in isolation

The effects of alaptide, a new analog of melanostatine, on self-stimulation of the lateral hypothalamus, rotation behavior in rotometer, and stereotypy were studied in rats bred in social isolation from other animals beginning from the 17th day of birth and rats bred in groups. Alaptide potentiated amphetamine-stimulated behavior only in rats reared in social isolation. This effect was lateralized: the left rotation dominated. In rats reared in isolation and in groups the effects of alaptide on self-stimulation were oppositely directed: in the former it increased and in the latter decreased the rate of self-stimulations with oppositely directed changes in pedal pressing duration. At the same time, alaptide suppressed the effects of amphetamine on self-stimulation of rats reared in isolation. The central dopamine mechanisms of melanostatine action are discussed.     

Septal nuclei in the mechanisms of lateral hypothalamic self stimulation in rabbits

Unilateral lesions of medial septal nucleus and lateral septal nuclei (dorsalis, intermedius, ventralis) decreased ipsilateral hypothalamic self-stimulation; the lesions of n. dorsalis, n. medialis and lateral septal nuclei (intermedius and ventralis) has the opposite effect on contralateral self-stimulation. The inhibition of ipsilateral self-stimulation was neither total nor permanent; 25-32% decrease in stimulation rate was seen, but behaviour returned to near-normal levels over a period of few days. In contrast, the augmentation of contralateral self-stimulation showed no significant change over the same period; in this case the 35-40% shift in stimulation rate was immediate and permanent. Bilateral lesions of septal nuclei had no effect if the initial level of self-stimulation rate was high and significantly increased self-stimulation.     

Change in the cholesterol and triglyceride content in the blood in self-stimulation and avoidance reactions]

The changes in the blood serum cholesterol and triglyceride content were studied or rabbits of both sexes during reactions of self-stimulation and avoidance. Self-stimulation was accompanied by a significant decrease in the blood serum cholesterol and triglyceride content. During the reaction of avoidance the character of the cholesterol changes varied. The reaction of avoidance of the "agression" type was accompanied by elevated blood serum cholesterol content, whereas the reaction of the "fear" type was associated with a decrease in its content. The maximal changes in the cholesterol and triglyceride content as compared to the initial level were observed in all types of the reactions 15--30 minutes following stimulation.     

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.     

Antistress effects of diazepam and activation of the positive reinforcing system upon changes on corticosteroid excretion and lipid level after peripheral electric pain stimulation]

It was shown in experiments on rats that the reaction of self-stimulation (SS) decreased the enhanced level of 11-hydrohycorticosteroids (11-HCS) in the blood after electrical pain stimulation(EPS) of the feet. Diazepam (1 mg/kg) decreased the levels of 11-HCS and beta-lipoproteids and increased the level of phospholipids after self-stimulation and pain stimulation. Diazepam and preliminary electrical pain stimulation induced activation of self-stimulation. It is concluded that diazepam and the activation of the positive reinforcing system exert similar effects on 11-HCS excretion and lipid levels after pain stimulation.     

Motivation dependence of brain self-stimulation in the pigeon

Several brain sites in the pigeon were identified as maintaining electrical brain self-stimulation. Depending on the site, stimulus currents yielding maximal responding varied from 20 to 160 μA. A high proportion of the sites only yielded self-stimulation behaviour if the subjects were deprived of food; when the birds were at full weight there was only one site at which the stimulation continued to be rewarding. Some, but weak, evidence of stimulus satiation was found. Overt behaviour elicited by non-contingent stimulation did not correlate with the reinforcing or neutral nature of the sites tested. While some positive sites were associated with structures known to be involved in the control of feeding, others were not. The hypothesis that stimulation at the hunger-dependent sites might have elicited temporary satiation signals is considered.     

Reinforcing stimulation of the postero-lateral hypothalamus and mating behaviour in the rat.

Male rats implanted with chronic electrodes into the postero-lateral hypothalamic site were tested for self-stimulation behaviour. Rats exhibiting steady self-stimulation behaviour were observed during mating tests with an oestrus female. During these tests the hypothalamus of male rats was stimulated. Results show that no stimulus-bound sexual behaviour was observed. Nevertheless, correlations were found between the rewarding value of the cerebral stimulation and the specific sexual components of mating behaviour. These results are interpreted with the hypothesis of a balancing effect between the reward elicited by direct stimulation of the brain and reward acquired by the presence of an oestrus female.     

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.     

The role of ACTH(5-8) and beta-MSH(5-8) fragments in the organization of the self-stimulation reaction

The experiments on rats have shown that intraperitoneal administration of ACTH5-8 fragments in a dose of 40 ng per kg altered considerably the character of self-stimulation reaction and the behaviour of rats. Searching activity and self-stimulation reaction were intensified, with the latter characterized by the onset of aversive components, that disappeared 24 hours later. Activation depended on the site of stimulation. Two phases of activity were noted (the first 0.5-1 h and the second 4.5-6 h after ACTH5-8 injection). beta-MSH5-8 fragment, when injected intraperitoneally in a dose of 20 ng per kg, had no effect on self-stimulation reaction and the behaviour of animals.     

The role of genetic factors in the determination of self-stimulation behaviour in the mouse: backcross analysis

Intracranial self-stimulation behaviour in the lateral hypothalamus was studied in male mice obtained from a backcross between the F1 generation BALB/c J × DBA/2 J and the strain BALB/c J, recessive for the majority of the self-stimulation parameters.The 48 animals of the backcross were divided into 3 groups at the 40 μ A intensity. One group of 11 mice had mean performances similar to those of the recessive parental strain BALB/c. This result suggests that the genetic determination of the difference of self-stimulation performances observed between BALB/c and DBA/2 strains is not very complex.A negative correlation appeared between the thresholds and the performances of self-stimulation.Finally, stimulation intensities above 40 μ A triggered convulsion with similar frequencies in the three backcross groups.     

Effect of stimulation of emotiogenic zones of the rat hypothalamus on the course of pregnancy and the growth of the progeny

The course of pregnancy and progeny development was studied in white rats with different emotional background during pregnancy. Self-stimulation of emotionally positive zones of the lateral hypothalamus and forced stimulation of emotionally negative zones of the ventral hypothalamus were taken as models of emotional states. Stimulation or self-stimulation of these structures, while causing unidirected negative effect on pregnancy and progeny, affected in different ways the speed of conditioning in viable progeny. Stimulation of emotionally negative zones of the ventromedial hypothalamus in the last third of pregnancy caused an acceleration of conditioning in the progeny. The self-stimulation of emotionally positive zones of the lateral hypothalamus failed to produce such effect.     

Opposite effects of cholecystokinin octapeptide (CCK-8) and tetrapeptide (CCK-4) after injection into the caudal part of the nucleus accumbens or into its rostral part and the cerebral ventricles

Neurons with colocalized cholecystokinin and dopamine are present predominantly in the ventral tegmental area and project mainly to the caudal part of the medial nucleus accumbens. The activity of this dopamine system can be evaluated by means of the intracranial self-stimulation behavior on male Wistar rats having chronic electrodes implanted into the medial forebrain bundle in the postero-lateral area of the hypothalamus. The direct injection of 150 pmol CCK-8 into the medio-caudal accumbens induced an increase of intracranial self stimulation while a similar administration into its rostral portion produced a slight decrease of intracranial self-stimulation. The administration of 300 pmol CCK-4 into the same medio-caudal part of the accumbens produced an inhibitory action on intracranial self stimulation lasting for 25 min. The injection of 70 to 1300 pmol CCK-4 into the cerebral ventricles produced no change on intracranial self-stimulation. The intracerebroventricular injection of 70 pmol CCK-8 induced a large decrease of intracranial self-stimulation lasting for 20 min. Sodium chloride 0.15 M or unsulphated CCK-8 injection were without effect in either case. These results support the ideas that intracerebroventricular CCK-8 injection inhibits accumbens dopaminergic activity but that CCK-8 injection into the medio-caudal part of the accumbens, where nerve terminals with colocalized CCK and DA are present, facilitates this dopaminergic activity. In addition at the level of medio-caudal accumbens, CCK-8 and CCK-4 have opposite effects.     

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.     

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.     

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.     

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.     

Autonomic correlates of the formation of a functional self-stimulation system

Capability of intracerebral electrostimulation to serve as an unconditioned reinforcing stimulus in classical conditioning was studied in rabbits. Changes of such vegetative characteristics as respiration frequency and ECG were taken as criterion of conditioned response (CR) elaboration. In preliminary experiments, optimal parameters of stimulation maintaining the highest level of instrumental self-stimulation behaviour were found for each of the animals. Isolated presentation of the unconditioned reinforcing stimulus led to the increase of respiratory rate. Such kind of stimulation induced tachicardia in 5 animals, bradicardia in 3 ones, and in the remaining 6 rabbits a biphasic reaction was observed with initial tachicardia changing for bradicardia. Reactions were taken as CRs if they were similar to those to the unconditioned stimulus and appeared at the moment of omitted reinforcement. After 10 pairings of conditioned sound stimulus with positive reinforcement, CR changes of the two vegetative parameters were observed in 21,4 per cent of cases. After 40 pairings CRs were observed in 87,5 per cent of trials for cardiac and in 78,5 per cent cases for respiratory components. The results obtained confirm the idea of validity and efficiency of intracerebral stimulation of self-stimulation zones as a factor of positive reinforcement.     

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.