Effect of intraventricular oxytocin and vasopressin on self-stimulation in rats.

Oxytocin (500 mu u) and vasopressin (50 mu u) were injected into the lateral ventricle and its effect on hypothalamic self-stimulation has been studied. Oxytocin increased, while vasopressin decreased the self-stimulation rate tested 10-20 min following application. The hypothalamic and mesencephalic serotonin content decreased slightly while plasma corticosterone content did not change 20 min after oxytocin and vasopressin administration compared to the injected control animals. The data suggest that vasopressin and oxytocin have an opposite effect on self-stimulation and this action is not mediated through the brain serotoninergic or pituitary-adrenocortical axis.     

ACTH fragments in compensation mechanisms of self-stimulation after ablation of the septal region in rabbits

Unilateral lesions of septal region, which partially included commissure anterior, commissural nuclei, fornix and apical parts of medial and lateral preoptic area, inhibited hypothalamic self-stimulation in rabbits. Intraventricular injection of ACTH (4-10) and ACTH (1-24) evoked the restoration of self-stimulation behaviour.     

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.     

Hypothalamic self-stimulation and stimulation escape in relation to feeding and mating.

This review begins with James Olds' discovery that self-stimulation at various brain sites can be influenced by food intake or androgen treatment. It then describes our research designed to reveal the functional significance of self-stimulation. The evidence suggests that lateral hypothalamic self-stimulation is controlled by many of the same factors that control feeding. We believe this control is exerted by at least two neural mechanisms. One is the classical, medial hypothalamic satiety system. Another is an adrenergic system ascending from the midbrain to the lateral hypothalamus. Damage to either one can disinhibit self-stimulation and feeding, thus contributing to obesity. Some of our studies use rats with two electrodes, one that induces feeding and one that induces mating. There are two response levers in the test cage, one for self-stimulation and one for escape from automatic stimulation. With the feeding electrode, rats self-stimulated less and escaped more after a meal than before. The same shift occurred after an anorectic dose of insulin or the commercial appetite suppressant phenylpropanolamine. With the sex electrode the shift from reward to aversion occurred after ejaculation. The review ends with credit to James Olds for pioneering this line of research into the neuropsychology of reinforcement.     

Direct current self stimulation in rats]

In experiments on 16 male albino rats a phenomenon of self-stimulation of the hypothalamic structures has been produced by a DC anode and cathode, with 20 to 100 microamperes intensity. DC self-stimulation consists in regular succession of approaching the pedal, staying on the pedal and leaving it, i. e. a succession of states of motivational drive, reinforcement and avoidance. In a number of cases the conditioned reflex of self-stimulation is not extinguished for two to three days after switching off the current.     

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.     

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.     

Action of naloxone on emotionally positive and antinociceptive effects of hypothalamic stimulation in rats

Naloxone (5 mg/kg subcutaneously) failed to effect significantly the reaction of electric self-stimulation in rats with electrodes implanted into lateral hypothalamic area. In 3 rats the analgesic effect manifested in an increase of the threshold of painful vocalization under electrostimulation of the tail was revealed. The antinociceptive effect was abolished with naloxone. Morphine (3 mg/kg) potentiated self-stimulation while naloxone antagonized this action. The role of opiate receptors in effects of self-stimulation and centrally produced analgesia is discussed.     

The self-stimulation reaction of rabbits in a helium-oxygen environment under increased pressure]

Change of intensity of hypothalamic self-stimulation was determined in rabbits during their stay in normoxic helium-oxygen medium under the pressures of 10, 15 and 40 kgf/cm2 at various speeds of compression. The experiments conducted testify to depressive influence on the hypothalamus self-stimulation of helium-oxygen medium under increased pressure; the influence was more expressed at higher pressures and great speed of compression. It is supposed that the decrease in frequency of pedal pressures was connected with the appearance of nervous syndrome of high pressures.     

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.     

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.     

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.     

Similar effect of caerulein on intracranial self-stimulation in vagotomized and non-vagotomized rats

Electrical stimulation eliciting self-stimulation behavior from postero-lateral hypothalamic implanted electrode was controlled by factors that control normal feeding. In this idea, lateral hypothalamic stimulation possessed an appetite whetting property and this is experienced as rewarding. The octapeptide cholecystokinin, a gut hormone, has been experimented upon to produce the complete behavioral sequence of satiety in rats. We observed that an i.p. injection of caerulein (an analog of cholecystokinin) did decrease, in a dose-related manner, the rate for brain self-stimulation. However, a similar effect on the rate of ICSS was measured after a bilateral cut of the vagus nerve at a subdiaphragmatic level. This result suggests that the decreasing effect on ICSS after an i.p. injection of caerulein is not strictly related to feeding. We interpret the decrease of reinforcement induced by caerulein as the action of a general satiety for any object presenting a rewarding value for behavior.     

The effects of feeding and fasting on self-stimulation

The effects of ad libitum feeding and 72 hr fasting on intracranial electrical self-stimulation behaviour (ICSS) were tested in cats. In contrast to previous studies it was found that the opposite manipulations in food intake, i.e. ad libitum feeding fasting, often induced identical changes in lever-pressing rate even in cases of lateral hypothalamic self-stimulation. Both increase and decrease in lever-pressing rate for ICSS could be observed depending rather on the electrically elicited behaviours than the precise anatomical location of the stimulating electrodes. It is concluded that changes in ICSS induced by food intake and food deprivation are probably secondary to the changes in activity level.     

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.     

Conjugation of the neuronal impulse activity in the rabbit neocortex during self stimulation of the lateral hypothalamus

Correlation of impulse activity of visual and sensorimotor neurons of both hemispheres in 10-s interval after self-stimulation of the right and left lateral hypothalamus was studied by plotting cross- and autocorrelation histograms. The number of cell pairs, in which sensorimotor neurons discharged after visual ones, increased after self-stimulation (from 24 +/- 6 to 44 +/- 7%). Frequencies of the alpha- and theta-range in crosscorrelograms increased; the alpha frequency increased mainly in the right hemisphere, while the theta frequency increased in the left hemisphere. The interhemispheric asymmetry in the interaction between cortical neurons was not associated with the side of hypothalamic stimulation.     

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.     

Cyclic nucleotides in the rat brain in the dynamics of hypothalamic self-stimulation

The content of cyclic nucleotides was measured in the brain structures of rats performing hypothalamic self-stimulation. Changes of the cAMP content were shown to possess a specific pattern corresponding to the features of self-stimulation. An increasing self-stimulation frequency (SSF) was followed by the maximum increase in the above index in the sensorimotor cortex; a stable SSF was accompanied by activation of the cAMP-dependent mechanisms of the septum, hypothalamus, and posterior hypophysis, while a decreasing SSF correlated with suppression of these processes in the septum, hypothalamus, and anterior hypophysis. Changes in the cAMP phosphodiesterase activity were less intensive and did not depend on the cGMP level. Changes in the cGMP content were nonspecific and unidirectional: this index increased, with the maximum at the stable self-stimulation mode. The ratio of cyclic nucleotides shifted toward cAMP when the SSF increased, and towards cGMP when the SSF decreased, while at a stable frequency their content was equal to the control level. The changes in the cyclic nucleotide contents were non-reciprocal (except an inverse correlation between their contents in the hypothalamus observed when the SSF dropped).     

Morphine-induced effects on the hypothalamic stimulation-evoked emotional/behavioral reactions and peculiarities of abstinent syndrome in adult and old rats

Experiments were carried out on adult young (6- to-9-month-old) and old (28- to-30-month-old) rats. The effects of a single i.p. injection of morphine on self-stimulation of the lateral hypothalamic region and on active avoidance responses evoked by stimulation of the ventromedial hypothalamic nucleus were studied. In a separate series of the experiments we studied age-related specificities of the abolition syndrome after a course of intraventricular injections of morphine. In most old rats single injections of morphine resulted in intensification of self-stimulation, while in most adult rats such injections suppressed this reaction. In old animals injections of morphine resulted in more pronounced increases in the threshold and latency of the active avoidance responses, as compared with similar changes in adult rats. Natural abolition of a 15-day-long course of injections of morphine resulted in the development of a characteristic abstinent syndrome that was more intensively manifested in old rats. Our results show that “hedonic” and anti-aversive effects of morphine increase with aging; this phenomenon probably facilitates the development of morphine dependence in old organisms.     

Disruptive effects of lateral hypothalamic stimulation on the lick-interrupt cycle in rats

Consummatory licking at a water spout was compared with licking at a dry spout maintained by electrical hypothalamic stimulation in the same rats. Both forms of licking, recorded photoelectrically, were maintained on a fixed ratio 8 schedule. Duration of reinforcement delivery was equated [300 ms]. A computer analysis of the temporal distribution of licks in each 1024 ms period from onset of reinforcement revealed that lateral hypothalamic stimulation decreased the occurrence of licking and disrupted the normally synchronous pattern of this behaviour. An analysis of the effects of delivering lateral hypothalamic stimulation contingent on water-maintained licking revealed that this effect of stimulation was clearly current-dependent. It is proposed that differences in licking rates maintained by water and by electrical hypothalamic stimulation, respectively, are due to response interference in the latter case. This interference effect is also proposed to be a major factor underlying higher reward thresholds for self-stimulation when licking is the operant response.