Combined effects of antiorthostatic suspension and ionizing radiation on the behaviour and neurotransmitters changes in different brain structures of rats.

Space flight factors (SFF) significantly affect the operating activity of astronauts during deep space missions. In contrast to an orbital flight, leaving the Earth's magnetic field is fraught with the dangers of exposure to ionizing radiation and more specifically, the high-energy nuclei component of galactic cosmic rays. Microgravity, just another critical non-radiation factor, significantly affects the normal functioning of the CNS. Some morphological structures of the brain, such as the prefrontal cortex and the hippocampus, that are rich in monoaminergic and acetylcholinergic neurones, are the most sensitive to the effects of ionizing radiation and non-radiation spaceflight factors (SFF). In this work we have studied the combined effects of microgravity (in antiorthostatic suspension model, AS) and irradiation (γ-ray and protons in spread-out Bragg peak) on the behaviour, cognitive abilities, and metabolism of monoamines and acetylcholine in the key structures of the rat's brain. Irradiation (as independently as combined with AS) resulted in the decrease of thigmotaxis in rats. Learning problems, caused by the malfunctioning of the working memory but not the spatial memory, were observed in response to AS as well as to the SFF in combination. Analysis of monoamines metabolism showed that the serotoninergic system was the most affected by the SFF. Concentration of acetylcholine in the hippocampus significantly increased in the groups of irradiated rats, and in the groups which were exposed to the SFF in combination, compared to the rats exposed only to AS.

[Motivation and Emotional States: Structural Systemic, Neurochemical, Molecular and Cellular Mechanisms].

The structural, systemic, neurochemical, molecular and cellular mechanisms of organization and coding motivation and emotional states are describe. The GABA and glutamatergic synaptic systems of basal ganglia form a neural network and participate in the implementation of voluntary behavior. Neuropeptides, neurohormones and paracrine neuromodulators involved in the organization of motivation and emotional states, integrated with synaptic systems, controlled by neural networks and organizing goal-directed behavior. Structural centers for united and integrated of information in voluntary and goal-directed behavior are globus pallidus. Substantia nigra pars reticulata switches the information from corticobasal networks to thalamocortical networks, induces global dopaminergic (DA) signal and organize interaction of mesolimbic and nigostriatnoy DA systems controlled by prefrontal and motor cortex. Together with the motor cortex, substantia nigra displays information in the brainstem and spinal cord to implementation of behavior. Motivation states are formed in the interaction of neurohormonal and neuropeptide systems by monoaminergic systems of brain. Emotional states are formed by monoaminergic systems of the mid-brain, where the leading role belongs to the mesolimbic DA system. The emotional and motivation state of the encoded specific epigenetic molecular and chemical pattern of neuron.

Integration the Highest Function of Brain as the Basis of Cognition.

Based on the process needs, motivations and emotions, are describing molecular, cellular and systemic mechanisms of goal-direction motivated behavior. Goal-direction behavior is impossible without the orientation in space and forming a cognitive map. This process implements the hippocampus, via the neocortical connections. The hippocampus is linked to the amygdala, which is involved in the implementation of emotional behavior and organizing emotionally intense cognitive map or context of the environment.

[Neurochemical mechanisms of a need, motivation and goal-directed behavior].

In this review is analyzed four kinds of needs, which include both humans and animals. These are: 1--the need to eat 2--need to drink 3--sexual need and, 4--the need to enhance or prolong the positive emotional state, and conversely, the need to dispose or avoid pain and unpleasant effects or negative emotional state. The centers of the first three needs are localized in the hypothalamus. The fourth need induced by integrative processes and determined the key role of the mesolimbic dopamine (DA) system of brain. Leptin and ghrelin, a hormone of satiety and hunger form of food motivation in neurons food center of the hypothalamus interacting with DA signal. Vasopressin, antidiuretic hormone, form drinking motivation in the neurons of hypothalamus drinking center interacting with DA signal. Vasopressin, oxytocin and steroid hormones form a sexual motivation in the neurons of the sexual center of the hypothalamus interacting with DA signal. Terminals of the mesolimbic DAergic system innervate hypothalamic neurons, amygdala, habenula and nucleus accumbens. The part of the neurons of amygdala and habenula respond to positive stimuli, and the other part to the negative stimuli. Integrative structure of mesolimbic DAergic system is the nucleus accumbens. GABAergic terminals of this nucleus terminate on exterior and interior nucleus of the ventral pallidum. Describes and discusses the emotional and motivational network and their interaction on the global DAergic signal.

Neurochemical and behavioral features in genetic absence epilepsy and in acutely induced absence seizures.

The absence epilepsy typical electroencephalographic pattern of sharp spikes and slow waves (SWDs) is considered to be due to an interaction of an initiation site in the cortex and a resonant circuit in the thalamus. The hyperpolarization-activated cyclic nucleotide-gated cationic I h pacemaker channels (HCN) play an important role in the enhanced cortical excitability. The role of thalamic HCN in SWD occurrence is less clear. Absence epilepsy in the WAG/Rij strain is accompanied by deficiency of the activity of dopaminergic system, which weakens the formation of an emotional positive state, causes depression-like symptoms, and counteracts learning and memory processes. It also enhances GABAA receptor activity in the striatum, globus pallidus, and reticular thalamic nucleus, causing a rise of SWD activity in the cortico-thalamo-cortical networks. One of the reasons for the occurrence of absences is that several genes coding of GABAA receptors are mutated. The question arises: what the role of DA receptors is. Two mechanisms that cause an infringement of the function of DA receptors in this genetic absence epilepsy model are proposed.

Asymmetry in dopamine levels in the nucleus accumbens and motor preference in rats.

Several studies on mice have demonstrated a correlation between the concentrations of dopamine and its metabolites in the nucleus accumbens and asymmetry in forelimb preference. Dopamine concentrations were greater in the nucleus accumbens ipsilateral in relation to the preferred paw. Limb preference was demonstrated in rats during performance of a response consisting of withdrawing food from a horizontal tube. Brain tissue dopamine concentrations were estimated by high-performance liquid chromatography with electrochemical detection. The results showed that in "left-handed" rats, the dopamine concentration in the left nucleus accumbens was significantly greater than that in "right-handed" rats. In right-handed rats, the dopamine concentration in the right nucleus accumbens was greater than that in the left. The results obtained here are significantly consistent with data obtained in mice and support the suggestion that the dopamine level in rats is greater in the nucleus accumbens ipsilateral to the preferred limb.

Pharmacological reminders of emotional state facilitate the retrieval of traces from amnesiac memory.

The experiments reported here show that animals with different levels of acquisition of a conditioned passive avoidance reflex retrieved the reflex differently on systematic testing over a period of 28 days. Animals with the highest and high levels of training reproduced the reflex stably. Animals with an intermediate level of training reproduced the reflex with significant variation. Convulsions induced by pentylenetetrazole (75 and 50 mg/kg. i.p.) resulted in amnesia. The amnestic effect of pentylenetetrazole convulsions depended on the ratio of the intensity of training and the intensity of the induction of convulsions. Reminding, provided by presentation of an unconditioned stimulus, removed the amnestic effect of the convulsive state. Training led to significant decreases in the parameters determining the severity of the convulsive state. The convulsive state was a dissociative state, as subconvulsive doses of pentylenetetrazole (30 mg/kg, i.p.) removed the amnestic effect of convulsive doses. The dissociated state was reproduced by pharmacological reminding of the state of anxiety and fear which was formed during training. A subcataleptic dose of haloperidol (0.25 mg/kg, i.p.) induced a state of fear and removed the amnestic effect of the convulsive state. The same dose of haloperidol improved retrieval of the reflex in animals with low levels of training, i.e., those in which retrieval hardly occurred in normal conditions.

Some neurotropic effects of low-intensity electromagnetic waves in rats with different typological characteristics of higher nervous activity.

The effects of low-intensity electromagnetic waves (4200 MHz, modulated with quasichaotic signals at 20-20,000 Hz, energy density 15 microW/cm2; specific energy absorption not greater than 15 mJ/kg) on the neurochemical systems of the brain and on behavioral reactions were studied in experimental animals with different typological characteristics of higher nervous activity. These studies showed that electromagnetic waves produced marked changes in the state and activity of the monoaminergic mediator systems which were in general terms concordant with changes at the integrative level (mostly selective inhibitory effects). The nature of these processes depended to a significant extent on the typological characteristics of the animals.

Synaptic vesicle acidification and exocytosis studied with acridine orange fluorescence in rat brain synaptosomes.

The acidification of synaptic vesicles (SV) in rat brain synaptosomes was studied using acridine orange (AO) as a fluorescent probe. In synaptosomal suspensions the AO fluorescence was partially quenched, indicating the presence of an acidic compartment. In permeabilized synaptosomes, the quenching was augmented by MgATP and was sensitive to concanamycin A, a specific inhibitor of the V-type H(+)-ATPase known to be present in synaptic vesicles. Some ATP-dependent acidification was also observed without permeabilization, suggesting that a fraction of synaptosomes (ca. 15%) was unsealed, irrespective of the method used to prepare the synaptosomes (sucrose or Ficoll density gradient, sedimentation or flotation). Depolarization of synaptosomes with 30 mM KCl resulted in an immediate, albeit small, rise in AO fluorescence that was prevented by the removal of Ca(2+) or by substituting NaCl for KCl. This response is consistent with depolarization-evoked release of the acidic contents of an exocytosis-competent pool of synaptic vesicles, representing ca. 5% of the total. No further AO release subsequent to the immediate phase was observed in depolarized synaptosomes, which indicates an extremely rapid reacidification. The results demonstrate that AO fluorescence is suitable for monitoring SV acidification within synaptosomes, and may be used to derive an independent estimate of the relative size of the immediately releasable SV pool. In addition, the use of AO might be advantageous for the assessment of synaptosomal integrity by comparing the ATP-dependent acidification in intact and permeabilized synaptosomes.

Long-term reduction of benzodiazepine receptor density in the rat cerebellum by acute seizures and kindling and its recovery 6 months later by a pentylenetetrazole challenge.

Seizures induced by an acute pentylenetetrazole (50 mg/kg) injection were accompanied by a long-term (at 1-48 h, but not on day 7) decrease in the density (B(max)) of [3H]-diazepam binding to benzodiazepine receptors in rat cerebellar cortex with no change in affinity (K(d)). Kindling for 24 days by daily administrations of pentylenetetrazole (20 mg/kg) led to the same decrease in benzodiazepine receptor density (at 1-48 h, but not on day 7) as that observed after a single dose of pentylenetetrazole (50 mg/kg). This suggests a common mechanism for both acute and kindling-induced seizures, dependent on the long-term receptor changes. The increased susceptibility to seizures persisted for 6 months after the termination of kindling, with BDZ receptor density in cerebellar cortex reduced almost by half. In age-matched controls, an acute dose of PTZ (30 mg/kg) induced seizures and decrease in both B(max) and K(d) of [3H]-diazepam binding. In kindled rats, at 6 months post-kindling, the same dose of PTZ (30 mg/kg) restored the benzodiazepine receptor density to the level found 6 months before, at the time of termination of kindling. Also, the severity of seizures was enhanced in the kindled rats. The results are discussed in terms of a balance of inhibitory and excitatory processes, in which the reduced BDZ receptor density at 6 months post-kindling may represent a compensatory reaction to outbalance some alterations in excitatory systems that have been reported to be induced by kindling.

Haloperidol catalepsy consolidation in the rat as a model of neuromodulatory integration.

Haloperidol, a non-selective D(2) dopamine antagonist, both in vitro (1 microM) and in vivo (2.5 mg/kg i.p.), induced a long-term potentiation of K(+)-induced Ca(2+)-dependent release of endogenous noradrenaline and dopamine in rat brain cortical slices, by increasing the content of noradrenaline and dopamine known to be controlled by dopamine auto- and heteroreceptors. Haloperidol administration (2.5 mg/kg i.p.) evoked catalepsy and increased the content of noradrenaline and dopamine in the same structures of the brain. Haloperidol catalepsy consolidated without any additional learning and could be retrieved up to two weeks later by placing the animals in the test box. The catalepsy is disordered and retrieved only in the test box. The catalepsy was more intense on day 14 than on day 7. Injection of haloperidol immediately after conditioning evened the reflex retrieval on the following days. Moreover, learning increased the intensity of catalepsy in animals tested on the day of injection. Repeated testing of the reflex on the following days led to specific modifications of catalepsy retrieval. Pre-conditioned rats exhibited maximal catalepsy when tested immediately after being placed in the test box. These results suggest that both the processes of long-term potentiation and catalepsy consolidation are mediated by the same type of receptors, long-term modulation-inducing receptors. Endogenous neuromodulators, acting non-specifically or diffusely via their respective long-term modulation-inducing receptors, can initiate and consolidate generalized states which form the basis for emotional and motivational states.

Relationship between the release and uptake of noradrenaline by rat brain synaptosomes in the formation of defensive conditioned reflex.

The defensive conditioned reflex with two-way avoidance was developed in rats in a shuttle-box. Immediately and 30 min after learning the animals were decapitated and synaptosomes were isolated from the whole brain and brain cortex. Using [14C] and [3H]-noradrenaline (NA), the processes of uptake, spontaneous and potassium depolarization-induced (60 mM KCl) release of NA by brain synaptosomes of trained and control animals were studied in vitro. Immediately after learning the inhibition of NA uptake was observed, but 30 min following learning the ability of synaptosomes to take up NA was recovered to the initial level. Thirty minutes after learning the potassium depolarization-induced release of NA previously taken up by synaptosomes increased as compared to the control. NA spontaneous release did not change under these conditions. With the increase of Ca2+ concentration in the incubation medium from 1.2 mM to 2.4 mM, the induced NA release from brain synaptosomes of trained and control animals regularly increased. Changes in NA release and uptake are specific for the development of conditioned reflex