Effect of the destruction of the brain serotoninergic system on the alcohol consumption by rats in the early periods of experimental alcoholism

Albino noninbred rats were divided into groups, according to the duration of alcoholic anesthesia (4.5 g/kg i.p.), of predisposed (195.6 min) and non-predisposed (69.1 min) to voluntary intake of alcohol. Another group included animals screened for 21 days according to the level of intake of 15% ethanol under the conditions of free choice between alcohol and water (6.15 and 2.62 g/kg pure ethanol per day, respectively). The animals were subjected to electro-coagulation of the dorsal or magnus raphe nucleus or were injected with 5,6-dihydroxytryptamine--DNT (75 micrograms/microliters) into the ventricles of the brain. It was established that in rats non-predisposed to alcohol intake, the destruction of the raphe nuclei, of the dorsal in particular, or injection of DOT to animals with a weak alcoholic motivation produces a dramatic increase in alcohol intake. In alcohol intake predisposed rats and in animals with a high level of alcohol use, analogous exposures do not bring about any significant differences in alcohol intake. The data obtained indicate that the reduced serotonin content in the brain is associated with an increase in the level of alcoholic motivation.     

The neurochemical and behavioral indices of an acquired alcohol craving in rats under conditions of information loading]

The state of neurotransmitter systems was studied in the groups of Wistar rats discriminated by striving for alcohol and rejecting it after the information load (alimentary instrumental conditioning in a labyrinth). The specific activities of neurotransmitter metabolizing enzymes (MAO A and B, acetylcholinesterase, and acetylcholinetransferase) and the content of biogenic amines and their metabolites (serotonin, 5-hydroxyindoleacetic acid, noradrenaline, and dopamine) were measured in homogenates and subfractions of sensorimotor cortex and caudate nucleus. It was found out that the biochemical indices correlated with cognitive abilities of animals. Stress-resistant rats, which were capable for acquisition of the complex skill, refused alcohol after the information load and were characterized by activation of the brain neurotransmitter systems. The rats, which were unable to fulfill the cognitive task, began to abuse alcohol and were characterized by suppression of the neurotransmitter systems. It seems possible that the brain neurotransmitter metabolism adequately reflects the characteristics of the higher nervous activity of animals and their resistance to alcohol.     

Alcohol and nicotine consumption exacerbates choroidal neovascularization by modulating the regulation of complement system

The objective of the present study was to investigate the effect of alcohol and nicotine consumption on the pathogenesis of choroidal neovascularization (CNV) in rats after laser-photocoagulation. Confocal microscopic analysis demonstrated an increase in CNV complex size in rats fed with alcohol (2.3-fold), nicotine (1.9-fold), and the combination of alcohol and nicotine (2.7-fold) compared with the control groups. Immunohistochemical analysis revealed that alcohol and nicotine consumption increased MAC deposition and VEGF expression in laser spots. Expression of CD59 by RT-PCR and Western blot was drastically reduced in the animals that were fed with alcohol, nicotine and alcohol and nicotine compared to those fed with water alone and this was associated with exacerbation of CNV.     

Effect of individual peculiarities on formation of preference of ethanol in female and male Wistar rats

Individual characteristics of animal behavior can serve a prognostic parameter of predisposition to use of alcohol. The goal of the work was to study dynamics of formation of preference of alcohol at early stages in the process of forced alcoholization in male and female rats as well as the accompanying changes in behavior parameters. For 3 months, the rats were submitted to the forced alcoholization with 10 % ethanol. Each week the rats were tested in the "two-glass trial". Individual peculiarities of all animals were evaluated prior to, after 6 weeks, and after the end of the experiment with aid of the "open field test" and "Suok-test". Results showed that the male rats demonstrating by the end of the experiment the significantly higher level of the alcohol preference, at the initial stages of the forced alcoholization demonstrated the significantly lower preference as compared with the remaining ones. These rats also showed the lower levels of the motor and exploratory activities before alcoholization as compared with control. On the contrary, the individuals that by the end of the experiment did not differ from control by the level of the alcohol preference demonstrated prior to alcoholization in the "Suok-test" the higher anxiety level. In female groups, no statistically significant differences were observed both in parameters of the motor and exploratory activities and in the anxiety level in both tests. Thus, in male rats, the prognostic parameter predicting formation of the abuse can serve the degree of alcohol preference at the initial stages.     

Adrenal glucocorticoid function in rats with various ethanol-induced sleeping time following ethanol administration

The effect of single and chronic ethanol (Eth) administration (25 % solution, 3.5 g/kg) on functional activity of the hypophyseal-adrenal system in rats with different sensitivity to the hypnotic action of ethanol (short-sleep - SS; non-sleep--NS, long-sleep--LS, intermediate group--IG), was studied. It has been shown that, after a single Eth administration, the concentration of corticosterone (K) in LS rat plasma was 1.5-fold higher than that in the NS animals although it did not differ from the K level in SS and Ig those. After repeated ethanol load, the corticosterone contents in the NS rat blood plasma was 3.5-fold and 4.9-fold lower compared to the control and LS groups, respectively. The data obtained indicate that the SS and LS animals had initially different basal blood plasma glucocorticoid level. The SS animals showed a decreased blood plasma K, whereas the LS ones--an increased one. The features of the glucocorticoid status are suggested to be a factor determining the sensitivity of rats to the ethanol hypnotic effect.     

The Sensitivity of Cognitive Processes to the Inhomogeneity of Natural Magnetic Fields

Three experiments were carried out to study the influence of inhomogeneity of natural magnetic field (MF) on animal cognition. Wistar rats (n = 90) were placed in a complicated problem environment, in which they were to form food-operant behavior under conditions of natural MF (Cond. 1) and MFs produced by iron objects (Cond. 2) or by magnets (Cond. 3). Unlike the control group (Cond. 1), all rats in Cond. 2 and 3 were unable to form operant behavior. Weak MF caused both locomotor and emotional depression, and there was no exploratory activity shown during 6 sessions. Brief external stimulation removed locomotor depression, and animals formed operant behavior similar to latent learning (Cond. 2) or “insight” (Cond. 3). Performance efficiency was lower while the level of stress manifestation was higher in Cond. 2 and 3 than in the control at the stage of stabilization. It has been proposed that MF reduces the activity of brain motivation centers and prevents the development of complicated forms of cognitive activity.     

Effect of taurine on cyclic AMP and GMP levels in the hearts of rats exposed to stress]

Taurine produced no effect on the cyclic nucleotides level in the heart of intact rats but sharply inhibited the cAMP and cGMP level elevation in the rat heart occuring in stress. After atropine pretreatment of the animals no effect of taurine on the heart cGMP level was observed; its effect on the cAMP level was significantly inhibited against the background of partial beta-adrenoreceptors block. It is suggested that taurine is a nonspecific regulator of the myocardial cells sensitivity to the biologically active drugs.     

Neuroactive steroids in the brain and age and sex specificity of behavior and anxiety: An experimental study

Changes in the brain’s neuroactive steroid levels, behavior in the open field, and the anxious-phobic status of male and female rats in the course of development have been studied. An increase in the motor and exploratory activity and emotionality in rats of both sexes in the pubertal period and a decrease in their values in mature and old animals have been detected. Anxiety has no sexual dimorphism in adult animals; it is significantly higher in males than in females in the prepubertal and pubertal periods of development and is higher in old females than in males of the same age. An increase in the level of corticosterone in some brain structures in maturing and old rats has been found; the testosterone concentration increases in one-month-old and adult animals but decreases in old individuals, while the estradiol concentration in all studied brain structures of male and female rats was low in all periods of postnatal life. Correlation analysis has shown modulation by steroid hormones of the changes in behavioral responses during development.     

Adaptive behavior of active and passive rats after intranasal administration of the corticotropin-releasing hormone

Behavioural effect of intranasal application of corticotropin-releasing hormone (CRH) was investigated in rats with high (KHA) and low (KLA) rate of learning in "open field" and plus-maze (PM) active avoidance test. The neurohormone provoked the opposed changes in behaviour of rats of this strain in both tests. The level of locomotion and exploratory activity rose in KLA rats and decreased in KHA rats. After the CRH application, the KLA rats but not KHA rats spent more time in the opened alleys of the PM than the control animals. The same behavioural changes were observed in our previous research when CRH was injected in striatum. We suppose that CRH is an endogenous factor of precise correction of the adaptive behaviour.     

Effect of the low-frequency impulse magnetic field on the autonomic nervous system in animals

The effect of weak (up to 3.5 mT) low-frequency (up to 100 Hz) impulse magnetic field on the state of the vegetative nervous system of animals has been studied by analyzing the variability of the heart rate. The effect of the magnetic field was estimated by a specially designed complex for recording cardiac signals of animals. Several specially selected regimes of impulse magnetic fields were studied. It was shown that the impulse magnetic field possesses a high biological activity at all regimes used, and the indices of the vegetative nervous system after the exposure to the impulse magnetic field approach the values typical for normotonic animals. This makes it possible to use magnetic fields at these regimes in magnetotherapy.     

Anticoagulation system in animals during learning under the effects of mild magnetic field and opioid peptide opilong

Information load in Wistar rats has not affected the functional state of the anticoagulant system after 20 sessions of learning to solve a food-searching task in comparison with intact animals. Learning under the combined effect of mild magnetic field and pretreatment with five intramuscular injections of an opioid peptide opilong has significantly improved the cognitive behavior but induced an increase in coagulation, imbalance in fibrinolytic processes, and inhibition of the anticoagulation system.     

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 AVP and DGAVP on the exploratory activity of rats

The effects of [8-L-arginine] vasopressin (AVP) and desglycinamide [8-L-arginine] vasopressin (DGAVP) were tested on the exploratory activity of adult male rats in a novel environment. The inherited individual differences in the non-specific excitability level of the animals were ascertained prior to the drug administration and the rats were then distributed evenly into the experimental groups. One half of each groups contained the less excitable and the other the more excitable animals. The peptides or saline were injected every other day--altogether 4 times--in a dose of 5 micrograms/kg/ml subcutaneously, 40 min before starting the experiments. The exploratory activity in the novel environment was observed for 15 min. AVP and DGAVP, which differ in their peripheral endocrine activities, had opposite effects on the behavior in a novel environment: AVP, with its wide spectrum of peripheral effects, decreased the exploratory activity, whereas DGAVP, with minimal peripheral effects, increased the exploratory activity slightly. This basic response to the administration of peptides was influenced by the type of inherent non-specific excitability level. The depressive action of AVP was more pronounced in the more excitable rats, whereas DGAVP significantly stimulated the less excitable animals. It is concluded that the inhibitory effect of AVP is mainly due to its peripheral endocrine, especially hemodynamic, effects, whereas DGAVP is supposed to increase arousal, which is responsible for differences in the animals' performance with regard to their inherited non-specific excitability levels.     

Liver alcohol dehydrogenase activity in the female rat: Effects of ovariectomy and estradiol administration

The effects of ovariectomy and administration of estradiol on the activity of liver alcohol dehydrogenase and on the rate of ethanol elimination were determined in female Sprague-Dawley rats. The activity of the enzyme and the rates of ethanol elimination in the female sham-operated animals were higher than obtained previously in male rats of the same age. Ovariectomy had no effect on liver alcohol dehydrogenase and on rates of ethanol elimination. Estradiol administration resulted in an increase in liver weight and in total liver alcohol dehydrogenase activity per animal in sham-operated but not in ovariectomized animals. The increase in enzyme activity after estradiol administration in sham-operated animals was not associated with a significant increase in the rate of ethanol elimination, suggesting that the enzyme activity in female rats is not rate-limiting in in vivo ethanol oxidation.     

Response of sensorimotor cortex neurons to weak disturbances of the magnetic field in Wistar rats. Cytochemical study

The influence of weak disturbances (up to 300 microT) of natural magnetic field on the protein metabolism in neurons of sensomotor cortex (layers III and V) in Wistar rats upon learning in a complex maze was studied. It was found that sensomotor neurons were very sensitive to weak disturbances of magnetic field. The protein content increased, while the nucleus-cytoplasm ratio and osmotic state of neurons remained unchanged. The specificity of neuron's reaction manifested itself in a sharp increase of nucleus and cytoplasm dimensions. In associative neurons (layer III), both the nucleus and cytoplasm were involved in the response; in efferent neurons (layer V), only nuclear parameters changed. The variance coefficients of all parameters of protein metabolism in sensomotor neurons, independently of their functional properties, were much higher than in control, which resulted in a wide diversity of cytochemical response.     

Age-related differences in serum melatonin and pineal NAT activity and in the response of rat pineal to a 50-Hz magnetic field.

In a previous study we have shown that exposure to a 50-Hz sinusoidal magnetic field decreased serum melatonin concentration and pineal enzyme activities in young rats (9 weeks). In the present study we looked for the effect of a magnetic field of 100 microT on serum melatonin and pineal NAT activity in aged rats and compared them to young rats. We hypothesized that aging may change sensitivity of rats to a magnetic field. Two groups of Wistar male rats [aged rats (23 months) and young rats (9 weeks)] were exposed to 50-Hz magnetic fields of 100 microT for one week (18h/day). The animals were kept under a standard 12:12 light: dark cycle with a temperature of 25 degrees C and a relative humidity of 45 to 50%. Control (sham-exposed) animals were kept in a similar environment but without exposure to a magnetic field. The animals were sacrificed under red dim light. Serum melatonin concentration and pineal N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT) activities were studied. Our results showed that sinusoidal magnetic fields altered the production of melatonin (28% decrease; P <0.05) through an inhibition of pineal NAT activity (52% decrease; P <0.05) in the young rats whereas no effect was observed in aged ones. On the other hand, when comparing data from control animals between young and aged rats, we observed that serum melatonin level and NAT activity, but not HIOMT activity, decreased in aged rats (decrease by about 38% and 36% respectively). Our data strongly suggest that old rats are insensitive to the magnetic field.     

Role of neuropeptide galanin in formation of the typical behavioural characteristics

Blockade of central galanin receptors through intranasal treatment with specific antagonis M-35 changes the behavioral reactions to novel conditions: the animals treated with M-35 show decreased exploratory activity and increased anxiety level in open field test. The level of pre-progalanin mRNA expression in brain structures was investigated in Wistar rats with opposite strategies of behaviors in open field test. A higher level of pre-progalanin mRNA in anterior hypothalamus of "active" rats was revealed as compared with "passive" rats. The rats treated with galanin receptor antagonist showed a significant rise of serum corticosteron level immediately after forced swimming, while the control rats (without M-35) had only slight corticosterone increase under the sam conditions. The data obtained suggest involvement of brain galanin in formation of individual beha vior and indicate important role of galanin in coping with the stress.     

Effect of individual peculiarities of emotional sphere on formation of preference of ethanol in female and male Wistar rats

Individual characteristics of animal behavior can serve a prognostic parameter of predisposition to use of alcohol. The goal of the work was to study dynamics of formation of preference of alcohol at early stages in the process of forced alcoholization in male and female rats as well as the accompanying changes in behavior parameters. For 3 months, the rats were submitted to the forced alcoholization with 10% ethanol. Each week the rats were tested in the “two-glass trial.” Individual peculiarities of all animals were evaluated prior to, after 6 weeks, and after the end of the experiment with aid of the “open field test” and “Suok-test.” Results showed that the male rats demonstrating by the end of the experiment the significantly higher level of the alcohol preference, demonstrated at the initial stages of the forced alcoholization the significantly lower preference as compared with the remaining ones. These rats also showed before alcoholization the lower levels of the motor and exploratory activities as compared with control. On the contrary, the individuals that by the end of the experiment did not differ from control by the level of the alcohol preference demonstrated prior to alcoholization in the “Suok-test” the higher anxiety level. In females there was observed a positive correlation of a decrease of the anxiety level in the process of alcoholization with a rise of ethanol consumption. Thus, in male rats, the prognostic parameter predicting formation of the abuse can serve the degree of alcohol preference at the initial stages.     

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.     

Acute and chronic dose of alcohol affect the load carrying capacity of long bone in rats

In the present investigation, the effects of acute and chronic dose of alcohol were evaluated on mechanical properties of long bones of Sprague Dawley rats. In "acute study", 18 animals were divided into three groups containing six animals each, i.e. Group A: control animals, normal saline was given to them intraperitoneally for the period of 5 days; Group B: treated animals, given 20% (v/v) absolute alcohol and Group C: treated animals, given 30% (v/v) absolute alcohol, by same route and time duration. In "chronic study", also, 18 animals were divided into three groups containing six animals each, i.e. Group A: control animals, normal saline was given to them intraperitoneally for the period of 6 weeks; Group B: treated animals, given 20% (v/v) absolute alcohol and Group C: treated animals, given 30% (v/v) absolute alcohol by same route and time duration. A significant increase was observed in bone weight of animals taking 20% alcohol but there was decrease in the same for 30% alcohol in case of acute study. For chronic study, there was a decrease in bone weight for both treated groups. During acute study, breaking strength of bone was increased in case of 20% alcohol administration but a slight decrease was shown in the same for 30% alcohol group as compared to control animals. Breaking strength of long bone in the case of chronic study was decreased in case of both groups taking alcohol, i.e. 20% and 30%. The present document is useful in understanding the functional load carrying capacity of bone during alcoholism.