The behavior of rats with different regimes of cerebral self stimulation]

The behaviour of rats was studied during electrical self-stimulation (SS) of the brain in a chamber with a pedal: with a fixed duration of stimuli trains (fixed SS regime), and in a self-controlled regime, where the duration of trains was set by the rat itself. As the current intensity or the duration of the trains continues to increases, the SS frequency in the fixed regime rises no longer. The duration of pressing becomes shorter than that of the trains, and the number of short pauses drops down to 50% of its total number of pauses, if at the same current intensity the duration of the train is the same or greater than that set by the rats in the self-controlled SS regime. With weak current intensities, the rats could fail to press the pedal if they received 0.1 sec. trains. But at the same current intensities the rats began SS, if they received for pressing the pedal a succession of trains of 0.1 sec. each with intervals of 0.1 divided by 0.2 sec. SS discontinued if the interval in the trains succession increased up to 0.4 sec.     

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.     

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.     

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.     

Behavioral, electrophysiologic and vegetative correlates of self stimulation in dogs]

Summary electrical activity of different brain structures (chiefly the hippocampal theta-rhythm) and cardiac and respiratory rhythms were recorded during self-stimulation (SS) in dogs. Emotional-motivational excitation in dogs, preceding SS, is attended with a moderate increase in theta-activity in the hippocampus. The SS period is characterized by desynchronization of the electrical activity, the appearance of high-frequency rhythmics and diminished theta-rhythm. After withdrawal of the pedal, hypersynchronization of the theta-rhythm sets in in most of the structures studied. SS is accompanied by considerable shifts of the cardiac and respiratory rhythms. The dynamics of behavioral, electrophysiological and vegetative shifts during SS in dogs points to a successive involvment of the brain mechanisms of search, positive reinforcement and emotional-negative interruption of the pedal pressing series. Complex interaction of the three mechanisms underlies the external phenomenology of the SS instrumental conditioned reflex.     

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.     

Amphetamine withdrawal: a behavioral evaluation

The effects of withdrawal from long-term amphetamine treatment of intracranial self-stimulation, forced swim-induced immobility, shuttle escape performance, acoustic startle and locomotor activity were evaluated. Mice implanted with stimulating electrodes in the lateral hypothalamus demonstrated stable and reliable rates of self-stimulation responding. After exposure to a chronic schedule of amphetamine treatment response rates were severely depressed. In addition to modifying intracranial self-stimulation responding, amphetamine withdrawal increased the duration of immobility in a forced-swim situation. Although chronic amphetamine exposure induced pronounced behavioral changes in the intracranial self-stimulation and forced swim tasks, drug withdrawal had little effect on shuttle escape performance, acoustic startle and locomotor activity. Based on these findings it was suggested that the development of post-amphetamine depression in the self-stimulation and forced swim paradigms was not related to variations in motoric or arousal mechanisms resulting from amphetamine withdrawal, but rather involved drug-induced changes in motivational processes.     

Cyclic analogs of ACTH fragments in self-stimulation and grooming behavior in rabbits

In present study new cyclic fragments of ACTH EHFRWGKPVG--NH2 and KHFRWG--NH2 were investigated in organization of self-stimulation and grooming behaviour in rabbits. Intracerebroventricular injections of EHFRWGPVG--NH2 in doses of 0.1-2.5 g evoked significant increases of self-stimulation and in doses of 4-5 g suppressed self-stimulation in rabbits. The effect of other fragments KHFRWG--NH2 on self-stimulation was not statistically significant. Both fragments induced excessive grooming behaviour in rabbits. The effects of these fragments persisted of 48-72 hours.     

Behavioral interactions in cocaine-treated rats

Effects of a single dose of cocaine (10 mg/kg,i.p.) were studied on spontaneous motor activity (SMA), stereotypy. self-stimulation of the posterior hypothalamus or area ventralis tegmentum (A10 area) and nonreinforced bar-pressing in rats. Interactions among these behaviors were investigated under different experimental designs. Cocaine caused an initial increase of SMA, which was later decreased significantly, as stereotypy became more prominent. Cocaine also caused facilitation of self-stimulation responding that further increased SMA. In both groups of self-stimulating rats, stereotypy disappeared completely during self-stimulation. Following cessation of self-stimulation, SMA and bar-pressing (that became nonreinforced) decreased, and stereotypy reappeared in both groups of rats.     

Discrete movements of foot epithelium during adhesive locomotion of a land snail

During the adhesive locomotion of land snails a series of short dark transverse bands, called pedal or foot waves, is visible ifa moving snail's ventral surface is observed through a sheet of glass. Moreover, the mucus secreted from the pedal glands and some pedal epithelial cells forms a thin layer which acts as a glue augmenting adherence, while also acting as a lubricant under the moving parts of the snail's foot. The relationships between velocity and the frequency of pedal waves as well as changes in the volume of small air bubbles under foot waves were analyzed by means of digital recordings made through a glass sheet on which the snails were moving. On the ventral surface of a moving snail foot, the adhering parts of the foot constituted about 80% of the total area, while several moving parts only about 20%. The single moving region of the foot (the pedal wave) amounted to about 3% of snail length. The epithelium in the region of the pedal wave was arched above the substrate and was also more wrinkled than the stationary epithelium, which enabled the forward motion of each specific point of epithelium during the passage of a pedal wave above it. The actual area of epithelium engaged by a pedal wave was at least 30% greater than the area of the epithelium as recorded through a glass sheet. In the region of the pedal wave, the tiny subepithelial muscles acting on the epithelium move it up in the front part of the wave, and then down at the end of the wave, operating vertically in relation to the substrate. In the middle part of the wave, the epithelium only moves forward. In summary, during the adhesive locomotion of snails, the horizontal movement of the ventral surface epithelium proceeds as temporally separate phases of upward, forward and downward movement.     

Intracranial reward after 5,6-dihydroxytryptamine: further evidence for serotonin's inhibitory role

One intraventricular injection of 50 μg of 5,6-dihydroxytryptamine produced, 24 hr later, a marked increase in rates of medial forebrain bundle self-stimulation. Whole brain serotonin levels were selectively depressed at this time, presumably because of the destructive effect on serotonin-containing neuron terminals. When whole brain serotonin levels had recovered fairly close to normal, the excitatory effect had disappeared. In rats having self-stimulation electrodes positioned at slight distances from the medial forebrain bundle, the excitatory effect never appeared. These results further support the theory that serotonergic neurons in the medial forebrain bundle are part of an inhibitory system subserving reward and motivational mechanisms. The results also again show the great importance of electrode placement as a determinant of a drug's effect on self-stimulation.     

Peptides and self-stimulation of the medial prefrontal cortex in the rat: effects of intracerebral microinjections of substance P and cholecystokinin

The effects of intracerebral microinjections of substance P and cholecystokinin on self-stimulation of the medial prefrontal cortex of the rat were studied. Intracerebroventricular administration of substance P at doses of 2.5, 5, 10 and 20 micrograms produced a dose-related decrease in self-stimulation of the medial prefrontal cortex; spontaneous motor activity, measured as a control, was not affected. Unilateral microinjections into the medial prefrontal cortex of substance P at doses of 10 and 20 micrograms produced a decrease of self-stimulation of the ipsilateral side, but self-stimulation of the contralateral cortex, used as a control, was not affected. On the contrary, cholecystokinin in both intracerebroventricular administration at doses of 100, 200 and 400 ng, or intracortical microinjections into the medial prefrontal cortex at doses of 200, 400 and 800 ng, had no effect on self-stimulation of this cortical area. These results suggest that substance P, but not cholecystokinin, could be part of the neurochemical substrate underlying self-stimulation of the medial prefrontal cortex in the rat.     

Long-term changes in self-stimulation threshold by repeated morphine and naloxone treatment

To analyse the interaction between endogenous opioid systems and brain reward, the influence of repeated treatment for 3 weeks with morphine and the opioid antagonist naloxone was investigated in rats with self-stimulation electrodes in the ventral tegmental area. Changes in threshold of self-stimulation determined by a response rate insensitive two lever method were considered as changes in reward. Morphine induced a temporary decrease of the response rate which lasted 3 days, and decreased the threshold for self-stimulation. The effect on threshold remained present till morphine treatment was discontinued, indicating that tolerance does not develop to this effect of morphine. Repeated naloxone treatment gradually increased the threshold for self-stimulation. This effect persisted after discontinuation of naloxone treatment. It is concluded that blockade of opioid receptors induces long term changes in the setpoint of self-stimulation reward.     

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.     

Measurment of pedal loading in bicycling: I. Instrumentation

This paper presents a new instrumentation system to precisely measure pedal loads and pedal position. A pedal/dynamometer unit implementing four octagonal strain rings measures all six load components between the foot and pedal. To study the relationship between foot position and loading, the pedal/dynamometer offers three degree-of-freedom adjustability. Pedal position along the pedal arc is precisely described by measuring crank arm angle and relative angle between pedal and crank arm. Linear, continuous rotation potentiometers measure the two angles. Transducer signals are sampled by a digital computer which calculates resultant loads and pedal position as functions of crank arm angle. Transducers are designed to mount on most bicycles without modification. Test subjects ride their own bicycles unconstrained on rollers so that loading data is representative of actual cycling.     

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.     

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.     

Effect of pedal rate on diurnal variations in cardiorespiratory variables

Recently, it was observed that the freely chosen pedal rate of elite cyclists was significantly lower at 06:00 than at 18:00 h, and that ankle kinematics during cycling exhibits diurnal variation. The modification of the pedaling technique and pedal rate observed throughout the day could be brought about to limit the effect of diurnal variation on physiological variables. Imposing a pedal rate should limit the subject's possibility of adaptation and clarify the influence of time of day on physiological variables. The purpose of this study was to determine whether diurnal variation in cardiorespiratory variables depends on pedal rate. Ten male cyclists performed a submaximal 15 min exercise on a cycle ergometer (50% W_max). Five test sessions were performed at 06:00, 10:00, 14:00, 18:00, and 22:00 h. The exercise bout was divided into three equivalent 5 min periods during which different pedal rates were imposed (70 rev · min^-1, 90 rev · min^-1 and 120 rev · min^-1). No significant diurnal variation was observed in heart rate and oxygen consumption, whatever the pedal rate. A significant diurnal variation was observed in minute ventilation (p=0.01). In addition, the amplitude of the diurnal variation in minute ventilation depended on pedal rate: the higher the pedal rate, the greater the amplitude of its diurnal variation (p=0.03). The increase of minute ventilation throughout the day is mainly due to variation in breath frequency (p=0.01)—the diurnal variation of tidal volume (all pedal rate conditions taken together) being non-significant—but the effect of pedal rate×time of day interaction on minute ventilation specific to the higher pedal rate conditions (p=0.03) can only be explained by the increase of tidal volume throughout the day. Even though an influence of pedal rate on diurnal rhythms in overall physiological variables was not also evidenced, high pedal rate should have been imposed when diurnal variations of physiological variables in cycling were studied.     

Effect of Pedal Rate on Diurnal Variations in Cardiorespiratory Variables

Recently, it was observed that the freely chosen pedal rate of elite cyclists was significantly lower at 06:00 than at 18:00 h, and that ankle kinematics during cycling exhibits diurnal variation. The modification of the pedaling technique and pedal rate observed throughout the day could be brought about to limit the effect of diurnal variation on physiological variables. Imposing a pedal rate should limit the subject's possibility of adaptation and clarify the influence of time of day on physiological variables. The purpose of this study was to determine whether diurnal variation in cardiorespiratory variables depends on pedal rate. Ten male cyclists performed a submaximal 15 min exercise on a cycle ergometer (50% W_max). Five test sessions were performed at 06:00, 10:00, 14:00, 18:00, and 22:00 h. The exercise bout was divided into three equivalent 5 min periods during which different pedal rates were imposed (70 rev · min^?1, 90 rev · min^?1 and 120 rev · min^?1). No significant diurnal variation was observed in heart rate and oxygen consumption, whatever the pedal rate. A significant diurnal variation was observed in minute ventilation (p=0.01). In addition, the amplitude of the diurnal variation in minute ventilation depended on pedal rate: the higher the pedal rate, the greater the amplitude of its diurnal variation (p=0.03). The increase of minute ventilation throughout the day is mainly due to variation in breath frequency (p=0.01)—the diurnal variation of tidal volume (all pedal rate conditions taken together) being non‐significant—but the effect of pedal rate×time of day interaction on minute ventilation specific to the higher pedal rate conditions (p=0.03) can only be explained by the increase of tidal volume throughout the day. Even though an influence of pedal rate on diurnal rhythms in overall physiological variables was not also evidenced, high pedal rate should have been imposed when diurnal variations of physiological variables in cycling were studied.     

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.