Functional transswitching of dominant motivation in the systems organization of behavioral acts

In experiments on rabbits, instrumental and complex conditioned alimentary behaviour was studied at various ways of raising alimentary motivation to extreme levels. Animals behaviour in these conditions could acquire an outwardly non-motivated (in relation to alimentary need) character. It is suggested that these phenomena are based on the transformation of the dominant motivation and not on the mechanism of "shifted" activity. In experiments on rats, a long "pseudoreinforcement" of extremely enhanced motivation of thirst by ethanol led to profound changes of physiological and neurochemical properties of the primary drinking motivation centres of the hypothalamus. It is suggested that such changes underlie the realization of plasticity properties of the dominant motivation.     

Effect of ethanol on the concentration of serotonin in the brain of the rat and the excretion of 5-hydroxyindoleacetic acid

It is found that serotonin content in the brain areas and heart of rats with low alcohol motivation decreases after 5 months of chronic consumption of 48% ethanol solution in a dose of 4 g/kg; in animals with high alcohol motivation serotonin content decreases only in the hypothalamus. Under chronic alcoholization for 1 and 12 months no considerable changes were found in serotonin level of the studied tissues. 60 min after intraperitoneal administration of 20% ethanol solution in a dose of 3 g/kg in intact animals there occurs an increase of serotonin content in the brain hemispheres and heart and its decrease in the hypothalamus; in rat with low alcohol motivation after taking ethanol for 5 months this administration evokes a decrease of serotonin content in the hypothalamus and truncus cerebri; in rats with high alcohol motivation--its decrease in the hypothalamus. Excretion of 5-oxyindoleacetic acid with urine decreases 10 months after alcohol intoxication. When rats were not given ethanol after its chronic taking for 3 months serotonin oxidation was intensified for the first day, which was not observed after 7-month alcoholization of animals.     

A comparative evaluation of alcoholic motivation in animals by 2 behavioral methods]

The attitude of outbred white male rats to alcohol was determined by means of two behavioural methods--the method of free choice of alcohol or water and of reaction of preference of place (PP) connected with taking of alcohol. Conclusion is made about greater adequacy of PP application for determination of alcohol motivation in animals.     

The effect of hypothalamic stimulation on food choice with rats maintained on different water-salt rations]

Electrical stimulation of the lateral hypothalamus in rats induces an increase of water intake and decrease of thresholds of eaten salty food. These effects are displayed in control animals and under salt diet and water deprivation. The hypothalamus stimulation relaxes the effects of "psychic distillation" of food which occur during spatial coincidence of conditioned signal of insipid food with salty reinforcement. Besides, the trans-switching of signal significance of conditioned stimuli connected with insipid and salty reinforcements is accelerated. The electrostimulation of the hypothalamus accelerates the elaboration of conditioned aversion of salty food inhibition of conditioned runnings toward corresponding food-box, and intensifies the existent state of thirst transforming it in the dominant motivation.     

Involvement of Serotonin in the Pathogenesis of Alcohol Addiction

We studied the contents of serotonin (5-HT) in a few brain structures (hypothalamus, midbrain, and neocortex) and in blood of rats with genetically determined preference of either ethanol solution or water as a liquid for drinking (groups preferring ethanol, PE, or preferring water, PW, respectively). Rats of the PE group differed from PW animals by significantly higher levels of 5-HT in the hypothalamus and blood. Peroral introduction of 4 g/kg ethanol into PE rats resulted in rapid (in not more than 15 min) sharp increases in the 5-HT content in the hypothalamus, neocortex, and blood, but 45 min after ethanol introduction the 5-HT contents in the hypothalamus, midbrain, neocortex, and blood noticeably dropped. It is suggested that within this time interval condensation of 5-HT with acetaldehyde (AcAdh, the first metabolite of ethanol oxidation) is intensified. This results in the production of -carbolines, analogs of morphine-like alkaloids, which are ligands of the opioid receptors. Under conditions of the development of alcohol addiction (free access of PE animals to the ethanol solution and water for several months), the content of 5-HT in the brain structures and blood increased in a parallel manner with an increase in the daily consumption of alcohol. Our findings are proof of the significant involvement of the serotoninergic system in the development of the euphoria state after single alcohol consumption and motivation for its consumption in the course of formation of alcohol addiction.     

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.     

The pathological dominant and the stable pathological state]

The pathological dominant is considered at a model of alcohol motivation which is in competitive relations with drinking motivation. The steady pathological state is considered at a model of seizure readiness in rats with audiogenic epileptiform seizures. The alcohol motivation might be ceased by the activation of competitive systems (thirst motivation), but the level of seizure readiness might be lowered intrasystemically, for example, by the habituation mechanisms.     

Role of limbic-neocortical mechanisms in the formation of experimental alcoholism in the rat

The role of the amigdalar complex and the hippocampus as well as their interaction with the hypothalamus in a formation of attraction to alcohol was studied in 40 rats. After electrolytic lesions of the hippocampus and the amigdalar complex at early stages of alcoholization the inhibition of development of this pathologic attraction occurred however with subsequent dynamical reorganization of the structural and functional mechanisms of alcoholic motivation and with duplication of the triggering links. Important role of the limbico-neocortical relations was revealed in a development of behavioural and emotional-vegetative disturbances accompanying experimental alcoholism.     

Electrophysiologic analysis of the conditioned reflex activity of cats against a background of thirst

EEG of the cerebral cortex and hypothalamic electrogram of cats during salt load and water deprivation were recorded at performance of conditioned running elicited by signals of insipid and salt food. The signal of insipid food presented during thirst was accompanied only by the cerebral cortex activation, while the salt signal involved in activation not only the cortex but the hypothalamus as well. In cases when the insipid signal was reinforced by salt food and the animal ate it (though during thirst it rejected the food), strong cortex activation was observed with the involvement of paraventricular parts of the hypothalamus. During intense thirst reversal was obtained of the signal role of the conditioned cue in accordance with the new quality of the alimentary reinforcement. Hypothalamo-cortical mechanisms of dominant motivation and its conditioned provision are discussed.     

Oligopeptides in the development of biological motivations

Data are presented, demonstrating the action of a number of oligopeptides on biological motivations of hunger, fear, self-stimulation and on alcohol addiction. In the structure of animals feeding motivation, such oligopeptides take part as beta-lipotropin and its fragments, ACTH, pentagastrin, delta-sleep inducing peptide (DSIP), substance P; in organization of defensive motivation--angiotensin II (AII), DSIP, substance P, bradykinin, beta-endorphin etc.; in organization of self-stimulation--AII, DSIP, bradykinin, ACTH, beta-endorphin etc. It is established that most of the above oligopeptides, injected to the brain lateral ventriculi, inhibit biological motivations, and only some of them have an activating action. On the basis of experiments, a hypothesis is formulated that oligopeptides act as a feedback between the genome of brain neurones and pacemaker cells of motivation centres of the hypothalamus area. Some oligopeptides elaborated by neuronal genomes under the action of dominating motivation, activate--and the other--suppress the activity of motivation hypothalamus centres.     

Effects of arginine-vasopressin and ACTH 4-10 on acquisition of active avoidance response in rats with alcohol pretreatment in prenatal and adult age

Alcohol administration in drinking water to mother rats during gestation resulted in a permanent learning deficit of the offspring when behavioural reactions were tested in active avoidance conditioned reflex situation in adult age. A similar deficit of learning capacity was observed in adult rats following alcohol administration for two weeks; the acquisition of active avoidance response was tested later. Administration of arginine-vasopressin and ACTH 4-10 during behavioural test led to a significant improvement of learning ability of the animals pretreated with alcohol. The observations indicate that the ethanol-induced deficit of learning capacity involves peptidergic mechanisms and the behavioural manifestations following chronic alcohol treatment are not irreversible processes.     

Elevated dietary salt suppresses renin secretion but not thirst evoked by arterial hypotension in rats

Increased dietary salt intake was used as a nonpharmacological tool to blunt hypotension-induced increases in plasma renin activity (PRA) in order to evaluate the contribution of the renin-angiotensin system (RAS) to hypotension-induced thirst. Rats were maintained on 8% NaCl (high) or 1% NaCl (standard) diet for at least 2 wk, and then arterial hypotension was produced by administration of the arteriolar vasodilator diazoxide. Despite marked reductions in PRA, rats maintained on the high-salt diet drank similar amounts of water, displayed similar latencies to drink, and had similar degrees of hypotension compared with rats maintained on the standard diet. Furthermore, blockade of ANG II production by an intravenous infusion of the angiotensin-converting enzyme inhibitor captopril attenuated the hypotension-induced water intake similarly in rats fed standard and high-salt diet. Additional experiments showed that increases in dietary salt did not alter thirst stimulated by the acetylcholine agonist carbachol administered into the lateral ventricle; however, increases in dietary salt did enhance thirst evoked by central ANG II. Collectively, the present findings suggest that hypotension-evoked thirst in rats fed a high-salt diet is dependent on the peripheral RAS despite marked reductions in PRA.     

Effect of etimizol on behavioral responses, brain serotonin concentration and plasma corticosteroid levels

The influence of ethymisol on behavioural reactions was studied on 100 albino rats in the "open field" and "passive avoidance" tests. It was shown that a 5 mg/kg dose of this neurotropic drug with synaptic effect, changes behavioural reactions, lowers the general emotional stress and emotional memory of the electro-cutaneous stimulation. Simultaneously the level of corticosteroids in the blood plasma significantly rises, while the serotonin content in the hypothalamus decreases. A direct correlation between the changes in the emotional stress and the content of corticosteroids in blood plasma is noted. The effects of ethymisol partially persists after adrenalectomy. Ethymisol in optimal doses may be used for regulation and lowering of emotional stress.     

Serotonin content in different sections of the brain, liver, intestines and blood of rats predisposed and not predisposed to alcohol consumption

Experiments were made with white random-bred rats (males) exposed to ethanol. The content of serotonin measured by spectrofluorometry was higher in the hypothalamus, brain stem and intestine, and was lower in the thalamus, striatum liver and blood in the animals predisposed to voluntary alcohol consumption and with lateral position duration 62 +/- 18 min as compared with the animals not predisposed to alcohol consumption and with lateral position duration 196 +/- 23 min, the dose of ethanol being 4.5 g/kg i. p. Thirty minutes after ethanol administration in a dose of 2.5 g/kg i. p. to the alcohol-predisposed rats there was a lowering of the serotonin content in the hypothalamus and an increase in the thalamus, brain stem, liver and blood. Meanwhile in the rats not predisposed to alcohol consumption, the serotonin content rose in the hypothalamus, brain stem, liver, intestine and blood and fell in the thalamus and striatum. It is assumed that the serotoninergic system of the brain may play a role in the formation of "positive" or "negative" attitudes to ethanol in the population of white random-bred rats.     

Behavioral models of the relation of animals to alcohol

Worked out on the outbred white male rats the behavioural models allow to pick out animals with initial alcohol motivation from the intact rats' group and to pick out animals with alcohol dependency and withdrawal syndrome from chronically alcoholized rats' group.     

Innate forms of behavior and energy metabolism in the brain of the rat after phenazepam administration in the presence of inescapable painful stimulation

Initially low level of motor search activity in test situations ("open field", maze) in rats previously grouped according to their passive behaviour with a partner-victim (Simonov method), does not essentially change after 3-week administration of phenazepam; the activity level of cytochrome oxidase in the cortex and hypothalamus is lowered. Phenazepam administration in conditions of prolonged unavoidable painful stimulation brings to a sharp increase of motor search activity and aggressive behaviour. Simultaneously the cytochrome oxidase activity increases in the same way as during a stress without phenazepam. This fact points to the independence of behavioural and biochemical effects in this case.     

Alcohol motivation in rats under blockade of protein synthesis by cycloheximide

The influence of protein blocker cycloheximide on the ethanol intake in alcohol-dependent rats was studied. It was found that intracerebroventricular as well as perifornical area hypothalamus injection of cycloheximide caused inhibition of ethanol consumption in alcohol-dependent rats, persisting for 5-9 weeks. The blockade action of cycloheximide was more strong after its injection in phase of decreased ethanol intake. At the same time it was shown an increase in water and food intake. The blockade action of cycloheximide on ethanol intake was not found in alcohol-dependent rats. These data indicate that some protein substances take part in mechanisms of organization of alcohol motivation and dependence.     

The role of the dopaminergic nigro-striatal system in aetiology of the lateral hypothalamic syndrome in cats (II): behavioural responses to regulatory challenges

Far-lateral hypothalamus ( FLH ) and substantia nigra (SN) were destroyed by means of radio-frequency current (RF lesion) or neurotoxically (6-hydroxydopamine injection) in 4 groups of cats. Deficits in osmoregulatory thirst were observed only after RF lesions of FLH . Disturbances in gluco-regulatory eating were observed after RF destructions and injections of 6-hydroxydopamine to the FLH . Both methods of SN damage did not affect the behavioural responses of the animals to regulatory challenges. These results suggest that deficits in behavioural responses to regulatory challenges observed in LH syndrome in cats are not related to the function of the dopaminergic nigro-striatal bundle.     

ACTH-induced excessive grooming in the rat: the influence of environmental and motivational factors.

Intraventricularly administered ACTHt_1–24 in rats initiated excessive grooming followed by stretching and yawning syndrome. The present study provides evidence that novelty is not an essential prerequisite for its expression and that a variety of environmental variables is not able to influence the peptide-induced behavior. Only very strong motivational variables as severe hunger/thirst and anxiety are able to modulate the ACTH-initiated excessive grooming: This response is significantly depressed in water-deprived rats bar pressing for water in a Skinner box, as well as in rats receiving unavoidable electric foot shock. The results are indicative of the strength of the ACTH-initiated motivation to groom, and it is suggested that excessive grooming is a secondary response serving to dearouse the organism after activation by ACTH.     

Possible correlations between the level of alcoholic motivation and the electrophysiological structure of sleep in the rat

Using modified Porsolt's method, the electrophysiological sleep pattern was studied in normal conditions and after a single intraperitoneal ethanol injection to noninbred male albino rats divided into 2 groups ("high activity" and "low activity" rats). Voluntary alcohol intake in these rats was measured during free choice between 10% ethanol and water for 20 days. "Low activity" rats were characterized by a statistically significant 3.4-fold higher level of ethanol consumption and 2.7-fold longer REM-sleep stage, as compared to "high activity" animals. In "low activity" animals ethanol (1 g/k, 10% solution, i. p.) inhibits and in "high activity" rats it increases REM-sleep stage, thus removing differences in the sleep pattern in the two groups of rats. The data obtained suggest a possible role of REM-sleep in the development of alcohol motivation.