Neurochemical analysis of the amygdala basolateral nucleus of rats during anxiety tests

Chlordiazepoxid, phenibut, indoter, campiron, campironin, when administered into the amygdala, improve the anxiety condition of rats in avoidance tests and resemble by their effects dophamine, GABA, or serotonin. Observed differences in the anxiolytic effects between anxiosedative and anxioselective agents seem to be due to an unequal contribution of the monoamin- and aminoacidotergic transmitters into the mechanisms of heteromodal aversive anxiety genesis in the basolateral area of the amygdalar complex.     

The role of neurochemical mechanisms of the dorsal raphe nucleus in various models of anxiety states in rats

Dopamine and serotonin microinjection in the dorsal raphe nucleus of rats does not influence the alarm state in the test of "threatening situation" avoidance, but increases or weakens the state of alarm in the rest of "illuminated site" avoidance. Local injection of GABA in this midbrain formation weakens the alarm state in the test of "threatening situation" avoidance but is not effective in the test of "illuminated site" avoidance. Chemical stimulation of the raphe nucleus by glutaminic acid does not influence the two different experimentally modelled states of alarm, but modulates the mechanisms controlling the instinct of darkness preference by rats.     

Neurochemical mechanisms of dorsal pallidum in antiadverse effects of anxiolytics of different models of anxiety

Microinjections of glutamine acid, serotonine and campiron into globus pallidus reveal antiadverse properties of ratsin in the test with avoiding "threatening situation" but not with "illuminated site" under the conditions of rats' free choice between light and dark sites. Dopamine, apomorphine, GABA, chlordiazepoxide, phenibut and indoter injected locally into this formation of basal ganglia do not affect the mechanisms of the involuntary movement, but counteract the conditions of anxiety in both models of behaviour. These results show different functional role of monoamino- and aminoacidergic systems of dorsal pallidum in operative regulation of behaviour with changing of aversive stimulus modality. Preliminary intraperitoneal injection of functional antagonists of investigated synoptotropic followed by microinjection of monoamines and amino acids into globus pallidus reveal selective involvement of neuromediator systems of dorsal pallidum into antiadverse anxiosedative and anxioselective actions.     

Effects of tranquilizing agents on bioelectrical activity of the rat brain]

The action of diazepam, meprobamate, trioxazine and mexidol on bioelectrical activity of sensorimotor cortex and dorsal hippocamp of the left and right hemisphere of the brain in conscious rat in free behavior has been studied. All the drugs produced a decline in the frequency of the dominant peak of EEG power spectra. Diazepam and meprobamate increased beta-activity. It is concluded that the decreased frequency may be due to an anxiolytic effect of the tranquilizers, whereas high beta-activity is related to muscle relaxant effect of some drugs.     

Role of the GABA-ergic link in the development of the tranquilizing effect in cats

The development of the tranquilizing effect of n-dipropylacetate (n-DPA) selectively increasing the GABA level in the nerve terminals was studied in experiments on cats in comparison with diazepam effect. The changes in the spectrum of emotional-behavioral reactivity were estimated. In doses of 50 and 200 mg/kg n-DPA caused a marked antiphobic effect which was not accompanied by the activating component characteristic of diazepam. The n-DPA-induced increase in the GABA level in the nerve terminals is suggested to be important for the development of the anxiolytic effect of tranquilizers. The total increase in the GABA level in the nerve terminals is suggested to be important for the development of the anxiolytic effect of tranquilizers. The total increase in the GABA content in the brain correlates to a greater extent with the sedative effect of drugs.     

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.     

Psychotropic effect of sodium hydroxybutyrate

A conclusion was drawn on the qualitative features of the spectrum of sodium hydroxybutyrate psychotropic activity from its effect on the conditioned motor-defensive reflex, behaviour in the conflict situation, active avoidance without discriminative control in rats as well as from the lateral position test The results obtained allow the effect of sodium hydroxybutyrate in non-narcotic doses to be characterized as a hypnotic one showing elements inherent in neuroleptics and tranquilizers.     

Hypoxic postconditioning corrects behavioral abnormalities in a model of post-traumatic stress disorder in rats

Protective effects of the novel technique of hypoxic postconditioning with a hypobaric hypoxia paradigm were studied in "stress-restress" model ofposttraumatic stress disorder in rats. It was shown that repeated (3 times) exposure of rats that survived after severe traumatic stress to mild hypobaric hypoxia (postconditioning mode) efficiently abolished the development of stress-induced anxiety state. Postconditioning had a clear anxiolytic effect both when it was delivered after traumatic stress and after restress, but the intensity of this effect depended on the period ofpathogenesis of the posttraumatic stress disorder, when postconditioning was given. The results indicate that suggested postconditioning model with repetitive mild hypobaric hypoxia exerts potent anxiolytic and stress-protective action.     

Individual sensitivity of Wistar rats to piracetam

Effects of repeated piracetam (PIR) injections in a dose of 40 and 250 mg/kg/day on the learning in Water rats were studied. It has been found that character of the effects depends on typological features of the animals. Rats with strong predominance of excitation (choleric type) showed low sensitivity to PIR. Small dose of PIR provoked clear negative effect in rats with relative balance of the basic nervous processes: excitation and inhibition (sanguine and phlegmatic types). Despite of expressed activation of associative process, it complicated integrative activity. Small dose of PIR showed anxiolytic and psycho-stimulant actions only in initially unlearned rats characterized by high level of fear. Large dose of PIR had negative influence on the learning process in all animals, irrespective of typological features. Thus, the results of this study allow to suppose that the individual sensitivity of an animal to action of a pharmacological medication is caused by morpho-functional and neurochemical intraspecific heterogeneity.     

Effects of the LHRH antagonist Cetrorelix on affective and cognitive functions in rats

The decapeptide LHRH antagonist, Cetrorelix, inhibits gonadotropin and sex-steroid secretion. Cetrorelix is used for IVF-ET procedures and for the treatment of benign prostatic hyperplasia, endometriosis and leiomyomas. However little is known about the effects of Cetrorelix on brain functions. Previously we have tested Cetrorelix in mice on the impairment of the consolidation of a passive avoidance behavior caused by beta-amyloid 25–35, anxiolytic action in the plus-maze, antidepressive action in a forced swimming test, tail suspension and open-field behavior following its administration into the lateral brain ventricle. In the present study we repeated and extended the experiments in rats in order to determine whether there are species differences in the action of Cetrorelix between mice and rats. The effects of Cetrorelix evaluated included the methods used in mice without tail suspension test and extended by measuring core temperature. Cetrorelix fully blocked the impairment of the consolidation of passive avoidance learning when given icv 30 min following administration of beta-amyloid 25–35. If beta-amyloid 25–35 and Cetrorelix were given simultaneously, Cetrorelix was ineffective. Cetrorelix elicited slight anxiogenic and stronger anxiolytic action in the plus-maze, depending on the dose used. In the forced swimming tests, Cetrorelix showed antidepressive-like action. In open-field behavior tests Cetrorelix displayed a U-type action on locomotion with 0.5 and 2 µg increasing locomotion, and increase rearing but and had no effect on grooming at 0.5–2 µg. Cetrorelix had no action on core temperature. Our findings demonstrate that Cetrorelix is able to correct the impairment of the memory consolidation caused by beta-amyloid 25–35. Cetrorelix elicits anxiolytic and antidepressive action, slightly increases locomotion and rearing in open field, but it does not influence the core temperature. The results obtained in rats are similar to those reported previously by us in mice. Collectively our findings confirm the effects of Cetrorelix on brain function in two species and suggest the possible merit of a clinical trial with Cetrorelix in patients with anxiety, depression and Alzheimer's disease.     

Effect of a change in the effectiveness of a benzodiazepine-GABA-ionophore complex blockade on the reproduction of an amnesic memory trace in mice after preliminary diazepam administration

The paper deals with the results of analysis of the influence of blocked of BD-GABA-ionophore complex and its separate components on recover of memory trace amnesia during BD-receptors activation in experiments on elaboration of CR of passive avoidance in mice. It is shown that at "neurochemical tuning" the improvement of conditioned reaction reproduction on the 2-nd and 21-st day after learning and amnestic action was observed only at GABAA receptor blockade by bicuculline, while the blockade of BD-receptor by flumazepil and of chlorine channel by picrotoxin was ineffective. Simultaneous blockade of all BD-GABA-ionophore complex components was not more effective in comparison with the blockade of its separate links in the recovery of conditioned reaction reproduction. The presented data allow to suppose that "psychogenic" amnesia development is determined by the functional state of neurotransmitter brain systems at learning and amnestic action which stipulates subsequent possibility of memory trace retrieval.     

The effect of single maximal physical loading on the emotional behavior of rats

In experiments on 250 Wistar female rats the influence was studied of a single maximum and submaximum physical loads on the emotional behaviour and the state of conditioned activity. It has been established, that as a result of maximum possible run of the animals depression takes place of orienting investigatory activity in conditions of the "open field" and disturbance of elaboration and reproduction of the conditioned reflex of two-way avoidance. Normalization of these parameters took place in 48 hours after the maximum load action. Analogous effect was observed in the period of aftereffect of the submaximum physical load, characterized by lowering of the level of behavioural activity in the "open field", disturbance of the elaboration of two-way avoidance as a result of presumable increase of functional tonus of the brain inhibitory systems.     

The effect of prolonged ethanol consumption on the physiological status and changes in brain peptidase activity of muricidal (aggressive) rats]

Muricidal and non-muricidal Wistar rats were studied regarding the changes of the body weight, the volume of the liquid intake, the sensitivity threshold to electrical shock, horizontal and vertical locomotor activity during 40-days period of 20% ethanol consumption. The transition to the situation of "choice" (water and/or ethanol) was accompanied by a division of the animals into two groups: "water preferring" and "ethanol-preferring" rats. The angiotensin-converting enzyme and enkephalin-forming carboxypeptidase H activity in different brain regions, hypophysis and peripheral tissues, were defined. The results allow one to conclude that neurochemical mechanisms underlying aggressive behavior (muricidity) and alcohol addiction have originally distinct nature.     

Behavioral differences between vasopressin-deficient (Brattleboro) and normal Long-Evans rats

Behavioral comparisons were made between rats of the Brattleboro strain with hereditary hypothalamic diabetes insipidus (DI) and normal Long-Evans rats. Measurements were made of activity behavior in a lighted open field and in a darkened activity chamber. Subtle measurement specific differences in the activity behavior of DI rats were found which suggested altered emotion, motivation and/or attention in the DI rats. In terms of learned behavior, DI and normal rats displayed a similar degree of habituation to all within-session activity measures in both the open field and darkened activity chamber. In a passive avoidance test, DI rats exhibited a degree of avoidance behavior equivalent to that of normal animals. Thus, these studies provide evidence that the vasopressin-deficient rat is not defective in learning and memory processes. The data can be interpreted as suggesting that vasopressin may influence memory tasks by extrinsic modulation of related states of emotionality, motivation and/or attention rather than by direct involvement in the retrieval and consolidation of information.     

Does deprivation of paradoxical sleep interfere with consolidation of memory traces?

The effect of paradoxical sleep deprivation (PSD) with water tank method on memory in the passive avoidance test as well as on open field behaviour was studied in rats. The effect of combining water tank PSD with a period of normal sleep-wakefulness cycle or with PSD non-emotional awakening was investigated in a special series of experiments. It is concluded that PSD, even by the water tank procedure, does not disturb trace consolidation and formation of long-term memory in the passive avoidance test. However, change in the correlation of motor-exploratory activity and fear reaction due to stress situation intrinsic in the water tank PSD procedure, does not allow the animals to reach comparatively long temporal criteria in the passive avoidance test.     

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.     

Emotional state variations in rats during recall of passive avoidance reactions after neurotensin administration into nucleus accumbens of the brain

Behavioral effects of neurotensin administration into the nucleus accumbens were studied in rats with neurotoxic lesions of serotoninergic structures of the dorsal raphe nucleus or periaqueductal grey matter. Changes in recall of passive avoidance conditioned reactions and aftereffects of painful stimulation in the locomotor activity were studied in the "open field" and elevated plus-maze and T-maze tests. The toxin administration into the dorsal raphe nucleus did not impair the recall of the passive avoidance reactions, but enhanced the oppressive aftereffects of painful stimulation, which can specify the development of anxiety in rats. The toxin administration into the periaqueductal grey matter had an opposite effect, which can be considered as a manifestation of the panic state. Neurotensin weakened the above mentioned effects of the toxin and, depending on the evoked emotional disorders, produced the anxiolytic or antipanic effects.     

Pharmacological correction of emotional stress after exposure to ionizing radiation and treatment with a radioprotector indralin

A possibility to use tranquilizers (aphobazole, phenazepamum) for reducing symptoms of prolonged emotional stress influencing rats after irradiation under treatment with a radioprotector indralin was investigated. It was found that indralin showed the protective effect and activated regenerative processes in the hemopoietic system of animals exposed to doses of 6.0 and 7.0 Gy. The prolonged emotional stress developing in the early periods after the exposure, essentially reduced the favourable action of the radioprotector on restoration of hemopoiesis. The application of tranquilizers stopped the inhibiting action of the emotional stress on the hemopoietic system of the irradiated animals in conditions of radioprotective administering.     

Buspirone: correlation of its anxiolytic and electroencephalographic effects

The influence of diazepam (1 and 5 mg/kg, i. p.) and buspirone (5 and 10 mg/kg) on the Fourier's spectral EEG power of sensomotor cortex and a conflict behavior in freely moving rats were studied. Diazepam (1 mg/kg) and buspirone (5 mg/kg) produced slowing of EEG theta-activity. Large doses of diazepam and buspirone produced different and multiple EEG effects. To 15-1788 (10 mg/kg) completely antagonized all the effects of diazepam (5 mg/kg). The authors discuss possible mutual relations between the influence on EEG and anxiolytic effect of these tranquilizers.     

Effect of previous experience in reacting to a danger signal on "open field" behavior in the rat

Modification of rats behaviour in an "hopen field" test was investigated, induced by an acoustic stimulus, previously subjected to conditioning in a shuttle chamber in experiments with possibility and impossibility of avoidance from electrical shock. It has been established that presentation of a stimulus having the meaning of a danger signal, in a new situation, significantly suppresses investigating behaviour of rats, whereas the stimulus which had not been subjected to conditioning exerts no marked effect on behaviour. The greatest suppression was observed in rats with "learned helplessness". This fact suggests that the degree of suppression of the behaviour in an open field in response to a danger signal, depends on the animal's previous experience in reacting to this signal.