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.     

Preference and aversion for brain stimulations estimated by the conditioned place preference

Rats implanted with chronic electrode into the medial forebrain bundle at the level of the hypothalamus (which elicited self-stimulation behaviour) display conditioned place preference after repeated stimulations of this area; conversely rats implanted into the mesencephalic dorso-medial tegmentum (which elicited switch-off behaviour) present conditioned place aversion after such repeated stimulations. Furthermore rats implanted in these two area without exhibiting self-stimulation or switch-off behaviours also display preference or aversion for the location paired with the brain stimulations. It was thus hypothesized that the conditioned place preference procedure seemed to present a higher sensitivity than the bar pressing procedures to detect preference or aversion for brain stimulation. Moreover the activation of the medial forebrain bundle which was associated with positive affect is more effective for a long term retention of the preferred location than midbrain periventricular reticular activation which induces a negative affect.     

Relations between stimulus-bound eating and intracranial reinforcing strength

Rats with monopolar electrodes implanted in the lateral hypothalamus were trained to self-stimulate, each under 38 different electrical stimulus values. Stimulus-bound drinking and eating (SBB) were elicited by stimulating the rats through the same electrode with the same parameters and the same rate at which they self-administered the stimulation.It was observed that the frequency of SBB depended on the parameters of the electrical stimulus. The Spearman rank order correlation was computed between strength of SBB and the strength of the reinforcing effect elicited by brain stimulation. A factor analysis showed that the reinforcing process elicited by brain stimulation in this area is composed of several factors and that SBB is not loaded in all the factors composing reinforcement.     

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.     

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.     

The role of biological needs in the genesis of self stimulation]

It has been found in fifteen rats with monopolar electrodes implanted in the lateral hypothalamus that after stimulation of the brain with bursts of electrical pulses of fixed duration, with definite combinations of stimulation parameters, the histograms of the duration of pedal pressing have a polymodal appearance. As the combinations of stimulation parameters change, the number, position and magnitude of the modes undergo a corresponding change. With unchanged parameters of stimulation the form of pressing duration histogram does not change significantly. A conclusion has been drawn that the modal duration of pressing in the course of self-stimulation is apparently an effector manifestation of central integration of reinforcing excitation. In a state of hunger and thirst as well as under weak nembutal anaesthesia, the previously monomodal histograms of the pressing durations produce additional modes which diminish and disappear after satiation and discontinuation of the nembutal effect. It is assumed that at least some modes of the histograms of the pressing duration of self-stimulation may reflect an activation of the systems of biological needs.     

Psychopharmacological analysis of hypothalamically-induced emotions

The effect of minor tranquilizers and neuroleptics was compared on self-stimulation and escape behaviourelicited by electrical stimulation of the hypothalamic nuclei in rabbits. It was shown that while tranquilizers (diazepam, oxazepam and meprobamate) increased the rate of self-stimulation elicited from the lateral hypothalamus, neuroleptics considerably suppressed such behaviour. Tranquilizers caused a remarkable reversal of the escape behaviour into a high-rate self-stimulation, both responses being induced from the same electrodes within the medial hypothalamus. Neuroleptics (chlorpromazine, reserpine and haloperidol) had not such an influence, though they somewhat increased the general activity of the animals. The reversing effect of the tranquilizers was compared with similar findings obtained after electrolytic ablation of the ventral hippocampus. It is suggested that the hippocampus has an inhibitory influence on the hypothalamic motivational system thus providing substantially for the animals' survival in a hostile environment.     

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.     

Peripheral and central mechanisms of the pressor response elicited by stimulation of the locus coeruleus in the rat

Electrical stimulation of the pontine nucleus locus coeruleus (LC) caused an increase of the arterial blood pressure in anesthetized rats, and elevated plasma noradrenaline (NA) and adrenaline (A) levels. The stimulation-induced pressor response was characteristically biphasic and consisted of a sharp rise in arterial pressure at the onset of the stimulation, followed by a second elevation at the end of the stimulus. Bilateral adrenalectomy or adrenal demedullation completely blocked the secondary phase of the pressor response elicited by stimulation, but did not affect the primary phase. The latter was specifically eliminated by the destruction of the peripheral sympathetic vasomotor axons with intravenous 6-hydroxydopamine (6-OHDA). The active sites eliciting the secondary adrenomedullary pressor component appeared to be restricted to the nucleus LC, whereas the primary sympathetic vasomotor response could be elicited from sites in and around the nucleus. After brain transection at the midbrain level, stimulation of LC failed to evoke the adrenomedullary pressor response, while the sympathetic vasomotor component was not affected. Similarly, destruction of brain NA neurons by intraventricular administration of 6-OHDA did not change the sympathetic vasomotor response, but virtually abolished the adrenal response. The results demonstrate that the pressor response to stimulation of LC in the rat is due to both increased sympathetic vasomotor activity and CA released from the adrenal medulla. The study also provides evidence suggesting that the noradrenergic LC cell group play an important role in the activation of the adrenal medulla, but is not essential for the activation of the sympathetic vasoconstrictor fiber system.     

Responses of bulbar neurons to stimulation of locomotor and inhibitory sites in the cat brainstem

Bulbar locomotor and inhibitory sites were located in the pons of mesencephalic decerebellate cats. Rhythmic stimulation of locomotor sites through microelectrodes at the rate of 60 Hz elicited stepping movements in the forelimbs which were halted when the inhibitory sites were rhythmically stimulated. Neuronal response was elicited by single or paired stimulation of locomotor sites at the rate of 1.5 Hz or by applying a series of 2–4 stimuli spaced 2 msec apart to the inhibitory site. Medial neurons generated synaptic responses (postsynaptic potentials or action potentials) to stimulation of the inhibitory site twice as frequently as when the locomotor site was stimulated. Responses in lateral neurons, however, occurred twice as frequently to stimulation of the locomotor site, while IPSP were only observed half as often as EPSP in neurons of both groups. In neurons excited by stimulation of the locomotor site, stimulation of the inhibitory site did not normally produce IPSP. Possible mechanisms underlying the halt of locomotion occurring in response to stimulation of the inhibitory site are discussed.Information Transmission Institute, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 18, No. 4, pp. 525–533, July–August, 1986.     

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.     

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.     

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.     

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.     

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.     

Model representation of rat motor behavior during electrical self-stimulation of the brain. I. Brief review of experimental data. Formal model]

The stimulation of the brain in self-stimulation situation activated the motor behaviour. The activity of the motor behaviour versus duration of the movements which define the motor activity is a decreasing function. The effect of stimulation versus duration or the strength of stimulation is an increasing function. The solutions of equation having made after comparing these two functions demonstrate the relations between the motor behaviour and stimulation parameters.     

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.     

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.     

Spatial cueing,sensory gating and selective response preparation: an ERP study on visuo-spatial orienting

Event-related brain potentials (ERPs) were recorded in a visuo-spatial attention task where the position of an imperative stimulus was indicated either validly or invalidly by a central arrow (trial-by-trial cueing). Subjects had to perform choice RT tasks with the response being dependent either on the identity of the target stimulus or on its position. When target identity was relevant for response selection, validly cued stimuli elicited amplitude enhancements of the early, sensory-evoked P1 and N1 components at lateral posterior sites. The N1 validity effect was limited to scalp sites ipsilateral to the visual field of stimulus presentation. Although these effects were found only when the sensory discrimination task was considerably difficult, they are in line with models assuming that modulations of sensory-perceptual processing (“sensory gating”) are induced by spatial cueing. However, when target location was response-relevant, N1 amplitude enhancements were consistently elicited by invalidly cued letters.CNV and LRP measures indicated that the arrow elicited response-related processing in the cue-target interval. Such processes occurred even when the cue contained no information about an upcoming response. Two consecutive lateralization phases were distinguishable in the LRP, with experimentally induced response assignments becoming effective only during the second phase.     

Respiratory resetting induced by spinal cord stimulation in the cat

Electrical stimulation (50-150 microA, 0.5-ms duration, 3-300 Hz) was performed within three different regions (lateral, ventrolateral, and ventral) of the C2-C3 spinal cord of decerebrate, vagotomized, paralyzed, and artificially ventilated cats. Spinal cord stimulation sites were located by inserting monopolar or bipolar stimulating electrodes either at the dorsolateral sulcus or at least 1 mm medial or lateral to the sulcus. With stimulation at each site, alterations in respiratory rhythm, orthodromic phrenic nerve responses, and antidromic activation of medullary respiratory-modulated neurons were examined. Phrenic nerve responses to cervical spinal cord stimulation consisted of an early excitation (2-4 ms) and/or a late excitation (4-8 ms). Stimulation of the lateral region evoked the greatest amplitude early response and stimulation of the ventrolateral region produced the greatest late excitation. All three stimulus sites elicited antidromic activation of some respiratory-modulated neurons in the dorsal (DRG) and ventral respiratory groups (VRG). The lateral region was the least effective resetting site, and it had the highest incidence of antidromic activation of both DRG and VRG neurons. The ventrolateral region of the cervical spinal cord was the most effective resetting site, but it had the lowest incidence of antidromic activation of DRG respiratory-modulated neurons. In addition, resetting responses were observed with spinal cord stimulation at similar sites in the thoracic and lumbar spinal cord regions thought to be devoid of inspiratory bulbospinal axons.(ABSTRACT TRUNCATED AT 250 WORDS)