The interaction of the serotonin and dopaminergic systems of the brain in the mechanisms of latent inhibition in rats

Decrease of serotonin concentration in the septo-hippocampal region of Wistar male rats was obtained by introduction of 5,7-dihydroxytryptamine in the raphe median nucleus. In seven days, after 20 pre-expositions of the conditioned stimulus (presentation of the experimental chamber) conditioned reaction of passive avoidance was elaborated. In sham-operated control the pre-exposition of the conditioned stimulus caused latent inhibition, determined by several parameters: low level of conditioned reaction reproduction, its prolonged preservation at the formed level and nonsubjection to amnesia. Introduction of haloperidol in a dose of 0.5 mg/kg one hour before learning restored the state of latent inhibition disturbed by switching off of the mesolimbic serotonin system. It is supposed that in the state of pre-exposition, the decrease of attention to nonreinforced stimulus takes place because of the intensification of inhibitory influence of the serotoninergic system and reciprocal decrease of dopaminergic system activity.     

Comparative analysis of the antiamnesic action of a blockade of the benzodiazepine-GABA-ionophore complex and of an activation of the dopaminergic system in the brain of mice

In experiments on mice by the method of conditioned reaction of passive avoidance and amnesia elicited by the animal delay in the dangerous compartment immediately after electrocutaneous stimulation, antiamnestic effect is demonstrated of pharmacological influences, changing the activity of benzodiazepine-GABA-ionophore complex and dopaminergic system. Comparative analysis of the efficiency of neuropharmacological substances of different actions on synaptic apparatus of the studied transmitter systems in amnesia reduction showed that the greatest effect of improving the reproduction of the conditioned habit was that of the bupropion, the highly specific blockator of dopamine reverse absorption. The obtained results testify that amnesia development is based on activation of the inhibitory GABAergic brain processes and disturbance of dopaminergic system functioning.     

Effect of successive lesions of the hippocampus and amygdaloid body on conditioned-reflex alimentary reactions in rabbits

Bilateral electrolytic lesions of the dorsal hippocamp and basolateral amygdalar complex impede the differential and extinctive inhibition. The damage of the corticomedial amygdala against a background of the dorsal hippocamp deficiency facilitates differentiation and extinction of alimentary reflexes induced by a decrease of the alimentary motivation and by weakening of alimentary conditioned reflexes. Lesions of the dorsal hippocamp after the corticomedial amygdala damage facilitates the training of positive alimentary reflexes, but weakens inhibitory conditioned reflexes.     

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.     

Fluorescence of dopaminergic terminals during elaboration of alimentary conditioned reflexes in the cat

A decrease of intensity of fluorescence of dopaminergic terminals in the nigrostriate and mesolimbic systems of rats was revealed under alimentary deprivation and during conditioned alimentary reaction. This decrease detected against the background of catecholamines synthesis blockade (alpha-methyl-para-thyrosine 40 and 80 mg/kg intraperitoneally) testifies to an activation of dopaminergic terminals and participation of nigrostriate and mesolimbic systems in conditioned alimentary reaction.     

Role of the amygdalar complex in programing of fast food-procuring movements in rats

Effects of uni- and bilateral electrolytic destruction of the basolateral nuclei of the amygdalar complex on the main parameters of fast food-procuring movements of albino rats were studied in the course of rearrangement of the motor programs; modifications of the parameters were observed both throughout the entire experiment and within each experimental day. The accuracy of the movements was significantly modified, which was manifested in an increase in the number of trials necessary for successful food capturing. An increase in the duration and a decrease in the frequency of the movements were also observed. The studied parameters underwent no complete recovery even on the tenth experimental day. Thus, the basolateral nuclei of the amygdalar complex occupy an important position in the system responsible for rearrangement of motivated automatized movements; when these nuclei are Injured, their function cannot be completely compensated by other brain structures.     

Effect of destruction of basolateral nuclei of the amygdala on the character of electrical activity of the dorsomedial thalamic nucleus in rats

Characteristics of slow global and of unit activity in the dorsomedial thalamic nucleus were studied at various times after destruction of nuclei of the basolateral amygdala in semichronic experiments on anesthetized rats. Destruction of this kind was found to cause periodic transformation of the neuronal discharge into rhythmic bursts of spikes, and into the development of bursts of paroxysmal activity in the form of groups of four to six pointed waves with a mean duration of 60.5±20.6 msec, appearing with a frequency of 1.5±0.3 Hz. A change in the coefficient of correlation was found between the duration of bursts and their frequency during the 20–22-sec period of their generation. Interference was demonstrated between bursts and orthodromic focal potentials, evoked by stimulation of the anterior periamygdalar cortex and anterior amygdalar region. Neurons were described with long (up to 1 sec) responses to stimulation of the periamygdalar cortex and amygdalar region, in the form of regular bursts of spikes or tonic activation, correlating with the appearance of a rhythmic after-discharge. Bursts of this kind, which were most marked during the first 3 or 4 days after destruction of the basolateral amygdala, were observed to begin to disappear toward the end of the first postoperative week. It is suggested that one mechanism of the change in the adaptive behavior of animals with destruction of the amygdala is a disturbance, linked with the bursts, of the relay and integrative functions of the dorsomedial thalamic nucleus.     

Ghrelin and Nicotine Stimulate Equally the Dopamine Release in the Rat Amygdala

The orexigenic peptide ghrelin plays a prominent role in the regulation of energy balance and in the mediation of reward processes and reinforcement for addictive drugs, such as nicotine. Nicotine is the principal psychoactive component in tobacco, which is responsible for addiction and relapse of smokers. Ghrelin and nicotine activates the mesolimbicocortical dopaminergic pathways via growth hormone secretagogue receptors (GHS-R1A) and nicotinic acetylcholine receptors (nAchR), respectively, resulting in the release of dopamine in the nucleus accumbens, the amygdala and the prefrontal cortex. In the present study an in vitro superfusion of rat amygdalar slices was performed in order to investigate the direct action of ghrelin and nicotine on the amygdalar dopamine release. Ghrelin increased significantly the dopamine release from the rat amygdala following electrical stimulation. This effect was inhibited by both the selective GHS-R1A antagonist GHRP-6 and the selective nAchR antagonist mecamylamine. Under the same conditions, nicotine also increased significantly the dopamine release from the rat amygdala. This effect was antagonized by mecamylamine, but not by GHRP-6. Co-administration of ghrelin and nicotine induced a similar increase of amygdalar dopamine release. This stimulatory effect was partially reversed by both GHRP-6 and mecamylamine. The present results demonstrate that both ghrelin and nicotine stimulates directly the dopamine release in the amygdala, an important dopaminergic target area of the mesolimbicocortical pathway.     

Changes in trace reactions of sensorimotor cortex and putamen neurons as affected by haloperidol

Experiments on conscious rabbits were made to elaborate motor conditioned reflexes through pairing stimuli with electrocutaneous reinforcement applied every 30 s. Neuronal activity in the sensorimotor cortex and putamen was recorded during formation and reproduction of the conditioned reflexes before and after haloperidol injection (0.2 mg/kg i. v.). In the putamen, haloperidol increased the number of neurons exhibiting trace conditioned activity and made the intensity and duration of these processes rise. The changes seen in the sensorimotor cortex were opposite in nature. Inhibition of trace conditioned activity in the sensorimotor cortex depended mainly on the decreased amplitude of the reaction conditioned component. The role of the dopaminergic system in the interaction of the neostriatum and sensorimotor cortex and in formation and reproduction of trace conditioned activity of both the structures is discussed.     

Formation of a conditioned "passive" avoidance reaction following ablation of the midbrain central gray]

Formation of conditioned "passive" avoidance reaction was studied in rats with a single pain reinforcement after electrolythic destruction of mesencephalic part of the central gray substance (CGS). The ablation of CGS ventral nuclei at the level of the midbrain rostral part led to a decrease in emotional reaction of "fears" and to disturbance of avoidance conditioning. The participation of midbrain limbic structures in learning and memory is discussed.     

Involvement of the brain dopaminergic systems in the development of the MPTP-induced depressive state in rats

Depressive state was produced in Wistar rats by repeated intraperitoneal administration of proneurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) inducing death of brain dopaminergic neurons. Weight loss and increase in REM-sleep rate during diurnal sleep were considered to be signs of the development of an experimental depressive state. During the development of the depressive state of rats, the MPTP-induced reorganization of the spectral power of electrical activity was observed in the terminal fields of the nigrostriatal, mesocortical, and mesolimbic dopaminergic systems, amygdala, and hippocampus. The most pronounced changes were revealed in the terminal field of the nigrostriatal system and hippocampus. The reorganization of the spectral power in the thetal and theta2 bands in the hippocampus and dopaminergic structures suggests the involvement of the hippocampus in producing changes in the emotional state during development of the MPTP-induced depressive syndrome.     

Changes in serotonin metabolism during food satiation in the mink and its effect on predatory aggression

Effect of single and protracted alimentary satiation on predatory aggression and content of serotonin and its metabolite 5-hydroxyindoleacetic acid in the amygdalar complex and hypothalamus was studied in mink--a representative of predators. A single alimentary satiation was not accompanied by any marked changes in serotonin metabolism and predatory behaviour. A long-term alimentary satiation significantly heightened the content of the 5-hydroxyindoleacetic acid in the lateral hypothalamus and amygdala without any changes in serotonin level, testifying to a high synthesis of serotonin with its simultaneous intensive destruction. Long-term satiation also greatly increased the latencies of aggression and killing the victim. It is suggested that serotonin is one of endogenous factors controlling predatory behaviour in predators, and this control is realized in interrelation with feeding behaviour.     

Critical review on quantitative autoradiography of D1 and D2 dopaminergic receptors in the striatum of the mammalian brain: differential localization and plastic changes after pharmacological manipulation and dopaminergic input disruption

Major technical progress in the development of computer-based image analysis systems has made possible the entry of autoradiographic and immunohistochemical techniques into a new era where quantification via densitometry and morphometry has become easily accessible. In this context, quantitative biochemical data can be adapted to anatomical and histological resolution. This adaptation is most efficient in the neuroscience fields because of the huge importance of cellular communication via neuronal networks in the nervous system. Therefore, any experimental approach to the brain which considers the brain as a 'black box' appears now as very crude. In fact, subtle heterogeneity in the distribution of biochemical markers can now be demonstrated, as illustrated here by the use of quantitative autoradiography of D1 and D2 dopaminergic receptors in the striatum of the mammalian brain. Also, local adaptive changes resulting from chronic blockade of the dopaminergic input can be detected after repeated treatments with dopaminergic antagonists selective for D1 or D2 receptors or with surgical lesioning of the dopaminergic nigrostriatal pathway. The resulting plastic changes are unevenly distributed throughout the striatal target organ and vary according to the mode of suppressing the dopaminergic flow: direct destruction of the dopaminergic pathway or selective pharmacological manipulation without physical elimination of the dopaminergic cells themselves. All these results are discussed and reviewed in light of the most recent reports in this field.     

Conditioned posture changes in dogs after systemic administration of dopaminergic agents

Influence of systemic injection of some dopaminergic drugs on conditioned postural rearrangement prior to instrumental movement realization and on other motor components of instrumental reaction as well as on the performance of the instrumental task itself--was studied in chronic experiments in 5 dogs on a model of instrumental defensive reflexes connected with maintenance of a certain posture. Drugs were used influencing the nigrostriate dopaminergic system, i.e. dopamine agonist L-DOPA and haloperidol blocking dopamine striate receptors. All the motor components of the instrumental reaction and first of all conditioned postural rearrangement were modified by systemic haloperidol injection. Initial components of the postural rearrangement were modified to the greatest extent, in particular the period of preparation of the animal to the posture change increased. On the contrary, the latency of initiation of postural rearrangement was sharply shortened by systemic injection of L-DOPA. On the other hand, the main component of the postural change, i.e. redistribution of body mass among the bearing limbs (the values of which significantly increased after preliminary stimulation of the head of the caudate nucleus) changed insignificantly during modulation of the striatum dopamine level.     

An analysis of the neuronal processes in the activating brain systems of the rat during the acquisition of an instrumental defense reflex

In chronic experiment, a defensive conditioned reflex was elaborated in rats with electrodes implanted in the reticular oral pons nucleus, cortico-medial group of amygdalar nuclei, ventromedial hypothalamic nucleus and central grey substance of the midbrain. Synchronization of the activity of neuronal groups of emotiogenic formations in the studied brain structures, became enhanced at formation of the conditioned reflex. A dependence was revealed of the level of correlation of limbic neuronal groups activity on functional state of the reticular formation, as well as neurochemical correlation mechanisms. The increase (decrease) of coefficients of correlation of the activity of neuronal ensembles of limbic structures was accompanied by a change of evoked potentials parameters recorded in them.     

The role of the dopaminergic system and GABA-benzodiazepine- ionophore complex in the regulation of memory retrieval

The spontaneous forgetting model has been used to demonstrate the possibility of the memory forgetten trace extraction under the dopamine reuptake blockade by nomifensine and bupropion, increase of its quantity by amfonelic acid, activation of the postsynaptic dopaminergic receptors by (+)3-PPP, blockade of the latter by (-)3-PPP, and under the blockade of separate links of the GABA-benzodiazepine-ionophore complex by bicuculline, picrotoxin, flumazepil and R015-3505. Effectiveness of the neuropharmacological actions improving the memory forgotten trace retrieval is shown to depend upon the duration of the spontaneous forgetting process. The presynaptic receptors are involved in the retrieval process control--improvement of the conditioned habit performance after forgetting due to the activation of presynaptic dopaminergic receptors by specific agonist (-)3-PPP is clearly correlated with the initial retrieval level. The above facts underlie a hypothesis about the neurochemical forgetting mechanisms.     

Food conditioned reflexes in dogs during activation and blockade of the cholinoreactive system of the amygdala

By means of chemical stimulation of subcortical structures it has been found that the cholinoreactive system of the basolateral part of amygdala is involved in realization of secretory component of alimentary conditioned reactions and takes no direct part in accomplishment of the instrumental component. Activation of the cholinoreactive system of the amygdalar basolateral part has an inhibitory effect and the blockade has an activating effect on the realization of the secretory component of alimentary conditioned reactions. A change in characteristics is observed of the differentiation inhibition and of the correlation of conditioned salivation in response to various stimuli presented in a stereotype order.     

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.     

Role of activity-dependent mechanisms in the control of dopaminergic neuron survival

Dopaminergic neurons that constitute the nigrostriatal pathway are characterized by singular electrical properties that allow them to discharge in vivo spontaneously in a spectrum of patterns ranging from pacemaker to random and bursting modes. These electrophysiological features allow dopaminergic neurons to optimize the release of dopamine in their terminal fields. However, there is emerging evidence indicating that electrical activity might also participate in the control of dopaminergic neuron survival, not only during development, but also in the adult brain, thus raising the possibility that alterations in ionic currents could contribute actively to the demise of these neurons in Parkinson disease. This review focuses on the mechanisms by which activity-dependent mechanisms might modulate dopaminergic cell survival.     

The remote consequences of hypoxia influence in perinatal development period on structurally functional characteristics of the rat brain

The study has shown that influence of acute hypoxia in perinatal period leads to structural changes in motor and visual of the neocortex for 20 postnatal days in the form of disturbance of the structural organisation of the neocortex layers. Different fields of hippocampus in perinatal period differently react to hypoxia, and evidence of existence of a long-term perinatal hypoxia was obtained. It is established that after action of acute hypoxia in all the fields there is a cellular destruction, and thinning of pyramidal neurones layers. The most expressed cellular destruction takes place in fields CA4 and CA3. In process of augmentation, the destruction of cells remains appreciable in the field CA4, reduced in the field CA3 and not found in the field CA1; however, in fascia dentate, the destruction of granular neurones with age augmentation increases. Along with in reduction of the dimensions of cellular bodies pyramidal neurones in all fields of hippocampus takes place. Also in all fields of hippocampus, activation of astrocytic reaction occurs, more expressed in the field CA4. The hypoxia influence in the early postnatal period can affect synaptogenes, particularly the formation of giant synapses in a dentate fascia. Study of functional features of the excitatory system of such animals has shown that hypoxia can induce appreciable disturbances of behavioural responses. In rats, disturbances of inhibiting functions of the cerebral cortex, raised anxiety, and spatial learning and working memory disturbances have been noted.