The effect of arginine vasopressin on the excitability and fatty acid content of the brain structures in rats with a neurosis

Experiments on rats with chronic bipolar electrodes implanted into the frontal cortex (FC), dorsal hippocampus (DH) and midbrain reticular formation (RF) established that the neurotic state (model "conflict of afferent excitation") was characterised by the increase in structure excitability: FC--15.4% (P less than 0.01), DH--12.4% (P = 0.05) and RF--17.5% (P less than 0.001). The presence of free fatty acids (FFA) revealed by chromatograph Schimadzu in brain cortex (BC), hippocampus (H) and midbrain (MB) in acute experiments evidenced the increase in the level of linolinic acid in all matters within the limits of 64-162% (P less than 0.05) and also different changes in arachidonic acid in BC and subcortical structures. The level of arachidonic acid increased by 120% (P less than 0.01) in BC but it decreased in H and MB within the limits of 34-56%. AVP (1 micrograms/kg) decreased excitability of FC by 6% (P less than 0.001), of H--by 8% (P less than 0.01) and RF--by 6%. In this case FFA, especially arachidonic acid, was increased in H and MB (by 2.5-6 times). The quantity of palmitic, stearic and oleic acids increased.     

Responses of neurons of the frontal area of the cortex of the rabbit to electric stimulation of certain limbic-mesencephalic structures after administration of substance P

In rabbits tested on behavioural reactions by electrical stimulation of certain limbic-midbrain structures, intravenous injection of substance P (30 mcg/kg) led after 10 min of silent period to a decrease of spontaneous neuronal activity in the frontal cortex. Convergence of excitations arising from the lateral hypothalamus, the dorsal hippocampus and the midbrain reticular formation was also found to decrease after the substance P injection. Analysis of neuronal responses allowed to establish that substance P markedly changed the ascending excitations of the lateral hypothalamus and was less effective for the influences from the midbrain reticular formation.     

Effect of lithium oxybutyrate on excitability of the cortex and some subcortical structures in rabbit brain

Lithium oxybutyrate microinjections (10 mg/ml) produce a depressant action on spontaneous bioelectrical activity of the cortex and subcortical structure. The drug brings down excitability of the motor cortex, hippocampus, caudate nucleus, thalamus, posterior hypothalamus and mesencephalic reticular formation; it also raises excitability of the tonsils. The depressant effect of lithium oxybutyrate is superior to that of lithium chloride.     

Reproduction of electrographic correlates of a conditioned reflex after changes in the activity of the noradrenergic and dopaminergic systems

On the model of shortly delayed defensive conditioned reflex in cats, it was shown in acute experiments that pharmacologically elicited change of NA system activity (clonidine, 0.2 and 1.5 mg/kg intravenously) and of DA system activity (apomorphine, 3 mg/kg intravenously) leads to a definite manifestation of electrographic correlates of memory trace, i.e. of conditioned evoked potential (EP) in examined brain structures, as well as of conditioned neurographic response (CNR) and conditioned skin-galvanic reaction (SGR). The increase of the NA system activity causes a rise of the number of conditioned EPs in the reticular formation, hippocampus and preoptic area along with an enhancement of CNR reproduction. The increase of the DA system activity contributes to the appearance of conditioned EPs in the hippocampus, amygdalar complex and central gray matter, together with an enhancement of the reproduction of conditioned SGR.     

Correlation between bioelectrical processes of the cortex, thalamus, midbrain reticular formation during formation of a defensive conditioned reflex in rabbits]

EEG power spectra of the sensorimotor area of the neocortex, the dorsal hippocampus, midbrain reticular formation and anteroventral thalamic nucleus, as well as corresponding coherence functions and phase spectra, undergo changes during formation and performance of defensive conditioned reflex in rabbit. The conclusion is draen that in the process of conditioning a morphofunctional system of brain structures is established including the above mentioned formations. Their functional integration occurs on the basis of theta-rhythm. The execution of a conditioned act requires isorhythmicity of electrical processes within the theta-range in the studied structures and an adequate level of their excitability, which is manifested in the dominance of 6,0 c/s frequency.     

Neuron activities of the motor cortex during conditioned eye blink reflex in rabbits (author's transl)]

Effects of the tone (CS) on neurons of the motor cortex were investigated in naive, pseudoconditioned, and conditioned rabbits. Conditioning to eye blink reflex was made by a combination of CS and air puff (US). Effects of electrical stimulation of the subcortical structures were also observed on the cortical neurons associated with the conditioned reflex. The results were as follows. (1) Proportion of neurons which significantly increased the firing rate in response to the CS, type E, was higher in the conditioned group than in other two groups. On the other hand, no group difference was found in the proportion of neurons which significantly decreased the firing rate to the stimulus, type I. (2) Most of the type E neurons in the conditioned rabbits began to fire at latencies of about 50 to 100 msec after the CS, preceding about 200 msec to the appearance of the peripheral conditioned responses (EMG). (3) Most of the type E neurons in the conditioned animals were more easily affected by stimulation of the medial geniculate body and the brain stem reticular formation. Based on the results mentioned above, it is concluded that in the rabbits conditioned to the eye blink reflex, excitability of neurons in the motor cortex is enhanced by the tone (CS), and by electrical stimulation to the medial geniculate body and the brain stem reticular formation.     

Characteristics of heterochromatin of heterophase nuclei from interphase neurons of various brain structures selected for the nervous system excitability

Quantitative characteristics (the area and number of chromocenters) of the interphase C-heterochromatin in the nuclei of pyramidal neurons of the midbrain reticular formation, sensorimotor cortex, and hippocampus (CA3) of rat strains with different genetically determined excitability were studied in the normal state of the animals and after exposure to a short-term emotional pain stress. The results indicate a relationship between the excitability of the nervous system and structural-functional state of the neuronal interphase heterochromatin. The role of cytogenetic features of different brain structures in the CNS functioning and behavior and their relation with genetically determined excitability of the nervous system are discussed.     

Intracerebroventricular injection of mu- and delta-opiate receptor antagonists block 60 Hz magnetic field-induced decreases in cholinergic activity in the frontal cortex and hippocampus of the rat

In previous research, we have found that acute exposure to a 60 Hz magnetic field decreased cholinergic activity in the frontal cortex and hippocampus of the rat as measured by sodium-dependent high-affinity choline uptake activity. We concluded that the effect was mediated by endogenous opioids inside the brain because it could be blocked by pretreatment of rats before magnetic field exposure with the opiate antagonist naltrexone, but not by the peripheral antagonist naloxone methiodide. In the present study, the involvement of opiate receptor subtypes was investigated. Rats were pretreated by intracerebroventricular injection of the mu-opiate receptor antagonist, β-funaltrexamine, or the delta-opiate receptor antagonist, naltrindole, before exposure to a 60 Hz magnetic field (2 mT, 1 hour). It was found that the effects of magnetic field on high-affinity choline uptake in the frontal cortex and hippocampus were blocked by the drug treatments. These data indicate that both mu- and delta-opiate receptors in the brain are involved in the magnetic field-induced decreases in cholinergic activity in the frontal cortex and hippocampus of the rat. Bioelectromagnetics 19:432–437, 1998. © 1998 Wiley-Liss, Inc.     

Quantitative and qualitative automatic evaluation of afterdischarges in the study of antiepileptic drugs

An automatic analysis of bioelectrical activity in some structures of the rabbit's brain was performed after i.v. administration of diazepam, phenytoin or phenobarbital. It was found that diazepam raised the ratio of fast activity in the afterdischarges pattern but paralelly decreased the total energy involved in the production of after-discharges in the cortex and midbrain reticular formation. Phenobarbital caused a significant shift in frequencies, increasing the ratio of slow activities (in the exception of hippocampus) and decreased the power spectra of afterdischarges in all structures (in the exception of midbrain reticular formation). Phenytoin, similarly to phenobarbital, decreased the ratio of fast activities. This effect was significant only in thalamus and midbrain reticular formation. At the same time it increased the total power of signal from hippocampus and midbrain reticular formation.     

Interrelations between neurons of the frontal cortex and hippocampus under cholinergic deficit in choice behavior of cats

Appetitive instrumental conditioned reflexes on light (CS+) were formed in six cats by the method of "active choice" of quality of reinforcement; bread-meat mixture was given after short-delay conditioned bar-press responses, and the delayed responses were rewarded by meat. The animals differed in choice behavior strategy: "self-control", "ambivalent", "impulsive". The multiunit activity in the frontal cortex and hippocampus (CA3) was recorded. Cross-correlation analysis was used for estimation of correlation of activities in neuronal pairs in the frontal cortex and hippocampus (distributed frontal-hippocampal networks) and pairs within the same structure (frontal and hippocampal local neuronal networks). It was shown that the number of cross-correlations between the discharges of neurons both in the local and distributed networks was significantly higher in "self-control" cats. Under conditions of systemic administration of antagonists of muscarinic central cholinoreceptors (trihexyphenidyl and scopolamine), the bar-press conditioning impaired, the number of direct interneuronal connections decreased, and the number of externally synchronized correlations ("common input") significantly increased. The results suggest that the local and distributed neural networks of the frontal cortex and hippocampus are involved in the system of brain structures that determine the behavioral strategy of "self control".     

Interaction of brain macrostructures during organization of behavior

The data on anatomical connections, injury consequences, summate and unit activity records may be represented as a chain of events running in sequence and in parallel in the brain of higher mammals. Internal (metabolism) and external (odour, pain, etc.) incentive unconditioned stimuli activate motivational structures of the hypothalamus, which in turn activates the frontal areas of the neocortex and the hippocampus. In case of coincidence of earlier neutral external stimuli with the action of reinforcing unconditioned ones, the hippocampus becomes the first place of convergence of combined afferentiations. After formation of the act, those external stimuli or their engrams which have been accompanied earlier by satisfaction of a certain need, are selected as a result of joint action of the hippocampus and the frontal cortex. By comparison of motivational excitation with available stimuli or their engrams retrieved from memory with the participation of the temporal cortex, an emotional colouring of the stimuli and engrams is formed in the amygdala leading to isolation of a dominant motivation, destined to be satisfied in the first instance. The program formed in the frontal cortex, comes to the basal ganglia where, by means of interaction with the parietal cortex, it confirms to the spatial coordinates of the forthcoming action. From the fronto-striate system, the excitation comes through the motor cortex to the effector organs accomplishing the behavioural act.     

Interaction between neurons of the frontal cortex and hippocampus during the realization of choice of food reinforcement quality in cats

Six cats were subjected to the procedure of appetitive instrumental conditioning (with light as a conditioned stimuls) by the method of the "active choice" of reinforcement quality. Short-delay conditioned bar-press responses were rewarded with bread-meat mixture, and the delayed responses were reinforced by meat. The animals differed in behavior strategy: four animals preferred the bar-pressing with a long delay (the so-called "self-control" group), and two cats preferred the bar-pressing with a short delay (the so-called "impulsive" group). Multiunit activity in the frontal cortex and hippocampus (CA3) was recorded via chronically implanted nichrome wire semimicroelectrodes. An interaction between the neighboring neurons in the frontal cortex and hippocampus (within local neural networks) and between the neurons of the frontal cortex and hippocampus (distributed neural networks in frontal-hippocampal and hippocampal-frontal directions) was evaluated by means of statistical crosscorrelation analysis of spike trains. Crosscorrelations between neuronal spike trains in the delay range of 0-100 ms were explored. It was shown that the number of crosscorrelations between the neuronal discharges both in the local and distributed networks was significantly higher in the "self-control" cats. It was suggested that the local and distributed neural networks of the frontal cortex and hippocampus are involved in the system of brain structures which determine the behavioral strategy of animals in the "self-control" group.     

Level of neuroactive steroids in the brain and sex-related peculiarities of formation and extinction of conditioned reflex in rats

Sex-related peculiarities of dynamics of brain sex steroids in the process of learning and extinction of the conditioned reflex of passive avoidance have been studied in model experiment. Prior to learning of the conditioned reflex, female rats were found to be distinguished by manifestation of anxiety and fear as compared with male rats. At formation of the conditioned reflex, no significant sex-related differences were detected between males and females, whereas extinction of the conditioned reaction of passive avoidance in males occurred by 2–3 days faster than in females. At learning of conditioned reaction of passive avoidance, in sexually mature male rats there was revealed an increase of the testosterone content in various brain structures, especially in hippocampus and frontal cortex, while its level in blood plasma remained unchanged. Also shown was an elevation of estradiol concentration in female amygdale, whereas at extinction of the conditioned reaction of passive avoidance, a rise of estradiol values was noted in hippocampus and cingular cortex. At the same time, the testosterone level in blood plasma did not change, whereas after extinction of the conditioned reflex the estradiol concentration decreased statistically significantly. Different dynamics of changes of the sex steroid levels in brain and blood plasma can indicate a possibility of their formation in the nervous tissue. The performed correlation analysis confirms the concept of selective involvement of testosterone and estradiol of individual brain structures in realization of processes of learning and memory in sexually mature male and female rats.     

Level of neuroactive steroids in the brain, and gender-related differences in formation and decrease of conditioned reflex in rats

We investigated gender-related differences in dynamics of the brain sexual steroids during learning and the decrease of conditioned reflex in the modeling experiment. It was revealed that, before training to conditioned reflexes, females manifested a greater anxiety than males. Significant differences between males and females in formation of the conditioned reflex of passive avoidance were not revealed, whereas the conditioned response decrease were by 2-3 days faster in male rats than in females. It was revealed that there was an increase of testosterone content in various structures of the brain, especially in hippocampus and frontal cortex with its constant level in the blood plasma in learning conditioned response of passive avoidance in male adult rats. Also an increased estradiol concentration was found in females' amygdale, while increased value of estradiol was detected in hippocampus and the singular cortex in decrease of the conditioned response of passive avoidance. In blood plasma, the testosterone level was not changed, and the estradiol concentration was reduced significantly after the decreased conditioned reflex. Different dynamics of changes in the levels of sex steroids in the brain and the blood plasma can indicate a probability of their formation in nervous tissue. The correlation analysis confirms the conception about selective involvement of the brain's testosterone and estradiol in the specific structures in realization ofthe learning and memory processes in adult male and female rats.     

The intercentral relations of the frontal cortex and limbic structures of the brain in dogs]

In 3 dogs with implanted electrodes, in conditioned experiments correlation of the bioelectrical processes was studied by coherence function calculation of the hippocampus, hypothalamus, amygdala and frontal cortex biopotentials. It was shown, that the level of maximum values of coherence function of bioelectrical oscillations, led from various pairs of the studied brain structures significantly differed both in magnitude and frequency at which the greatest synchronization of biopotentials was noticed. In one dog with a high degree of connection between the hippocampus and hypothalamus biopotentials oscillations, a low synchronization of the frontal cortex and amygdala oscillations was found; in two other animals with a higher level of coherence between the oscillations of the frontal cortex and amygdala biopotentials, a lower degree of connection between the oscillations led from the hippocampus and hypothalamus was revealed. Synchronization of the biopotentials of the hippocampus and frontal cortex and also of the hippocampus and amygdala biopotentials proved to be low in all experimental dogs, what additionally testifies to different role of these structures in organization of the behaviour.     

Acute cocaine treatment increases thimet oligopeptidase in the striatum of rat brain

Many studies indicate that thimet oligopeptidase (EC3.4.24.15; TOP) can be implicated in the metabolism of bioactive peptides, including dynorphin 1-8, α-neoendorphin, β-neoendorphin and GnRH. Furthermore, the higher levels of this peptidase are found in neuroendocrine tissue and testis. In the present study, we have evaluated the effect of acute cocaine administration in male rats on TOP specific activity and mRNA levels in prosencephalic brain areas related with the reward circuitry; ventral striatum, hippocampus, and frontal cortex. No significant differences on TOP specific activity were detected in the hippocampus and frontal cortex of cocaine treated animals compared to control vehicle group. However, a significant increase in activity was observed in the ventral striatum of cocaine treated-rats. The increase occurred in both, TOP specific activity and TOP relative mRNA amount determined by real time RT-PCR. As TOP can be implicated in the processing of many neuropeptides, and previous studies have shown that cocaine also alters the gene expression of proenkephalin and prodynorphin in the striatum, the present findings suggest that TOP changes in the brain could play important role in the balance of neuropeptide level correlated with cocaine effects.     

Shifting of the brain stem physiological impedance after ovariectomy and oestradiol implantation in rabbits

Experiments were carried out on female rabbits with electrodes implanted chronically into the midbrain, dorsal hippocampus and the cerebral cortex. Physiological impedance of the brain stem, i.e. the lowest energy of trains of electric impulses stimulating the midbrain modulated through a feedback by the hippocampal theta rhythm and maintaining EEG arousal pattern, served as a measure of excitability of the brain stem reticular formation. After ovariectomy performed in 12 female rabbits, a rise in the brain stem physiological impedance was observed in relation to control measurements -- by 84.8%, on the average. In 8 ovariectomized female rabbits the physiological impedance decreased by 47.4% after subcutaneous implantation of oestradiol benzoate tablets. After removal of the implanted tablets the impedance increased by a mean value of 100.1% in all the female rabbits.     

The effects of acute ethanol exposure and ageing on rat brain glutathione metabolism

Binge alcohol consumption in adolescents is increasing, and it has been proposed that immature brain deals poorly with oxidative stress. The aim of our work was to study the effect of an acute dose of ethanol on glutathione (GSH) metabolism in frontal cortex, hippocampus and striatum of juvenile and adult rats. We have observed no change in levels of glutathione produced by acute alcohol in the three brain areas studied of juvenile and adult rats. Only in the frontal cortex the ratio of GSH/GSSG was increased in the ethanol-treated adult rats. GSH levels in the hippocampus and striatum were significantly higher in adult animals compared to young ones. Higher glutathione peroxidase (GPx) activity in adult rats was observed in frontal cortex and in striatum. Our data show an increased GSH concentration and GPx activity in different cerebral regions of the adult rat, compared to the young ones, suggesting that age-related variations of total antioxidant defences in brain may predispose young brain structures to ethanol-induced, oxidative stress-mediated tissue damage.     

The effects of acute ethanol exposure and ageing on rat brain glutathione metabolism

Abstract

Binge alcohol consumption in adolescents is increasing, and it has been proposed that immature brain deals poorly with oxidative stress. The aim of our work was to study the effect of an acute dose of ethanol on glutathione (GSH) metabolism in frontal cortex, hippocampus and striatum of juvenile and adult rats. We have observed no change in levels of glutathione produced by acute alcohol in the three brain areas studied of juvenile and adult rats. Only in the frontal cortex the ratio of GSH/GSSG was increased in the ethanol-treated adult rats. GSH levels in the hippocampus and striatum were significantly higher in adult animals compared to young ones. Higher glutathione peroxidase (GPx) activity in adult rats was observed in frontal cortex and in striatum. Our data show an increased GSH concentration and GPx activity in different cerebral regions of the adult rat, compared to the young ones, suggesting that age-related variations of total antioxidant defences in brain may predispose young brain structures to ethanol-induced, oxidative stress-mediated tissue damage.