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Comparative analysis of behaviors of two rat strains, Wistar and WAG/Rij, was performed. No behavioral differences between Wistar and WAG/Rij were found in the emotional resonance test. Disulfiram injection produced similar effects in both rat strains. Animals of the first group (with slow acquisition of emotional resonance reaction) transformed into the animals of the second group (with fast acquisition). Passive avoidance conditioning was successfully reproduced in Wistar and was significantly impaired in WAG/Rij. A low dose of disulfiram injected before or immediately after conditioning substantially improved the reproduction to a greater extent in WAG/Rij than Wistar strains thus eliminating in interstrain differences. Active avoidance conditioning was more successful in WAG/Rij than in Wistar rats However, on the next day conditioning in WAG/Rij was substantially impaired. Administration of the low dose of disulfiram or L-DOPA prior to conditioning impaired the acquisition but improved the reproduction on the following day in both strains, but disulfiram injection after conditioning improved conditioning in WAG/Rij to a greater extent than in Wistar. Thus, the pharmacologic enhancement of the reward system substantially changed animal behavior and improved memory consolidation.

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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.

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Typological behavior reactions of WAG/Rij rats were studied from the standpoint of divergent modulatory integration hypothesis. This rat strain has a genetically determined dominant dysfunction of the benzodiazepine system of the thalamic nuclei. This disorder provokes an epileptiform disease such as absence epilepsy. It was suggested that the dysfunction of this system would result in a modification of the modulatory systems, which support the motivation states of escape and avoidance reactions as well as of the modulatory systems, which form the emotional states. Modifications of these states are the background of typological behavioral features of WAG/Rij rats. It was shown that WAG/Rij have the lower threshold of the development of haloperidol catalepsy, higher levels of fear and depression. On the first day of training in a shuttle box, WAG/Rij rats demonstrated better avoidance performance than Wistar rats. On the second and 28th days, the amnestic effect of the epileptiform disease was observed. The amnestic effect was also observed after passive avoidance conditioning. The results are discussed in terms of the modulatory integratin hypothesis.

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Rats were divided in two groups by the reaction of emotional resonance (RER): with emotionally positive reactions (I, with fast RER acquisition, up to 100 s) and with emotionally negative reactions (II, with slow RER acquisition, more than 200 s). After the RER acquisition, the activity of 5-hydroxitryptophan (5-HT) system of the I group of animals was lower than in the II group. The activity of noradrenaline (NA) and dopamine (DA) systems of the I group of animals was higher than in the II group. The between-group differences were enhanced by subcutaneous injection of dalargin. In some brain structures dalargin reversed these relations. These findings point to a complicated interpenetrating character of emotionally positive and emotionally negative states. Emotionally positive states include components of emotionally positive states, and emotionally negative states include components of emotionally positive states. Increase in 5-HT activity and decrease in activity of NA, DA, and opioid (OP) systems induce formation of emotionally negative states. Decrease in 5-HT activity and increase in activity of NA, DA, and OP systems induce formation of the emotionally positive state. It is suggested that 5-HT, NA, and DA systems play the central role in the processes of reinforcement, acquire the evaluative function, and are included in realization of all types of behaviors. OP is a primary modulator system which accompanies the unconditioned pain stimulus and connects it with systems of evaluative function.

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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.

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Passive avoidance reflex was shown to be differently reproduced in rats. The reproduction was more stable in rats with a higher level of learning. Amnestic effects induced seizures were shown to depend on relationships between the intensity of learning and the intensity of seizures. Unconditioned stimuli acting as a reminder decreased the amnestic effects of seizures. Learning process significantly reduced the seizure severity. A dissociated convulsive state was reproduced with the aid of a pharmacological reminder of anxiety formed in the course of learning. Haloperidol produced anxiety and suppressed amnestic effects of seizures, facilitated conditioning in rats with a low level of learning.

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In rat brain cortex, haloperidol initiates the long-term potentiation of K(+)-induced Ca(2+)-dependent noradrenaline (NA) and dopamine (DA) secretion in vitro and in vivo. In both cases, the long-term potentiation is caused by the long-term increase in catecholamine content in the NA and DA terminals, as it has been shown in cortical tangential slices. Acute intraperitoneal haloperidol injection (2.5 mg/kg) evokes catalepsy and increases the content of NA and DA in the brain structures with localization of catecholamine receptors on terminals. This increase appears to be caused, predominantly, by modification of the terminal DA receptors, since only a trend to catecholamine increase is observed in the brain structures with a mixed type of NA and DA receptor localization (on somata and terminals). It is suggested that the long-term and diffuse action of haloperidol after its acute administration consists in the anxiogenic reaction and consolidation of catalepsy without an additional procedure of training and in the absence of unconditioned stimulus.

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Catalepsy induced by a single intraperitoneal injection of haloperidol (2.5 mg/kg) was consolidated and without additional influences and retained within 2 week (being tested on the 2nd, 7th, and 14th days after injection). Enhancement of catalepsy retrieval was observed during testing of the same animals on the 14th day as compared with the 7th day. Maximal catalepsy expression was reached after 2 hours of testing procedure which points to the existence of the mechanism of autoenhancement of retrieval which is probably underlain by the automodulation of the long-lasting modulatory DA receptors. The retrieval of catalepsy is suggested to be induced by a situational conditioned stimulus, since on the 2nd, 7th and 14th days it may be reproduced without repeated haloperidol injection only in the testing box.

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Influence of 5-hydroxytryptophan (5HTP) and disulfiram on a reaction of emotional resonance (RER) was studied in two groups of female rats: I--with good and II--with poor elaboration of RER and, correspondingly, with the minimal and the maximal time of stay in the dark compartment. One week after 5HTP injection good elaboration of RER in animals of the I group was substituted for poor. In the II group of animals RER was unchanged. Injection of disulfiram increased the stay in the dark compartment in the I group and decreased it in the II group. At the same time dopamine content in the midbrain and medulla increased. The results confirm the hypothesis on participation of monoamines and their different contribution in RER realization in different groups of animals.

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The content of norepinephrine (NE) and serotonin (5-HT) in the right and left halves of the brain of rats was compared in the norm, during the development of defensive two-way avoidance conditioned reflexes (TWACR), and with the administration of peptides which influence learning and memory, namely desglycine-arginine vasopressin (DG-AVP), ACTH4-7 pro-gly-pro, and dalargin. These investigations demonstrated that the content of NE in the right cerebral hemisphere is significantly higher than in the cortex of the left. Significant differences were not detected with respect to the 5-HT content in symmetrical parts of the brain. The asymmetry of the NE content was eliminated under the influence of the development of the TWACR. The systemic administration of DG-AVP, ACTH4-7 pro-gly-pro, and dalargin essentially did not alter the 5-HT content, and decreased the NE content in the cortex and in the rest of the brain. In the process the NE content of the right and left hemisphere evened out. The data obtained point to the asymmetrical character of the action of the neuropeptides and to the greater resistance of the serotoninergic system of the brain to a functional load and the administration of peptides by comparison with the noradrenergic system.

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Content was compared of noradrenaline (NA) and serotonine (5-OT) in the right and left halves of the rats brain in norm, at elaboration of defensive conditioned reflexes of two-ways avoidance (CRTWA) and at administration of neuropeptides influencing the learning and memory--dezglycilargininvasopressin (DG-AVP), ACTH4-7 pro-gli-pro and dalargin. The conducted studies showed that in control animals the content of NA in the cortex of the right hemisphere was significantly higher than in the cortex of the left one. For the content of 5-OT in symmetric brain parts no significant differences were revealed. Under the elaboration of CRTWA the asymmetry of NA content was not eliminated. Systemic administration of DG-AVP, ACTG4-7 pro-gli-pro and dalargin practically did not change the content of 5-OT, but reduced the content of NA in the cortex and the rest of the brain, and the content of NA in the right and left cortex was equalized. The obtained data point to the asymmetric character of neuropeptides action and to greater resistance of 5-OT-ergic brain system to functional load and to administration of peptides in comparison with NA-ergic system.

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In experiments on outbred female rats the influence was studied and compared of two representatives of endogenous opioids beta-endorphine and the analogue of leu-enkephalin dalargin on the processes of learning and memory in normal conditions and at the change of functional state of serotoninergic system of the brain. Parallel, the influence was studied of neuropeptides on the content of serotonin (5-OT) and its metabolite--5-oxyindolacetic acid in various areas of the brain in control and at the 5-OT redundancy. Conditioned reflexes (CRs) were used of two-way avoidance and defensive CRs. It has been established that administration of neuropeptides to intact animals influences in different directions the elaboration of the CR of two-way avoidance and maze defensive CR, but also worsens their preservation. Redundancy of 5-OT in the brain modifies behavioural effects of beta-endorphine and dalargin manifested in appearance of new effect and elimination and change of direction of the effects observed in the intact animals. Redundancy of 5-OT in the brain changes metabolic effects of beta-endorphine and particularly of dalargin. The obtained data testify to a dependence of the effects of beta-endorphine and dalargin on the functional state of 5-OT-ergic system.

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On the basis of the idea of the important role of neurotransmitter systems in realization of neuropeptide effects, the participation was studied of the monoaminergic systems in the mechanisms of the ACTH analogue influence on the processes of learning and memory in control animals and animals with a changed functional state of the monoaminergic systems. In parallel the influence was studied of the ACTH analogue on the content of the endogenic monoamines in various brain structures of rats. It has been shown that administration of the ACTH analogue in a dose of 10 mcg affects the elaboration and preservation of conditioned reflexes (CRs) of passive avoidance, CRs of two-side avoidance and labyrinth CRs only in conditions of changed functional state of the monoaminergic systems. Amnesia, usually elicited by 5-oxytryptophane and disulfiram is prevented by administration of the ACTH analogue. Administration of the ACTH analogue is accompanied by the intensification of serotonine metabolism in the midbrain and medulla and by an increase of noradrenaline content in the hypothlamus.

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The levels of water-soluble brain antigens have been studied during bilateral avoidance learning in Wistar rats. With the help of cross and rocket immunoelectrophoresis the content of antigens was measured in the brain structures an hour and a week after training. It was shown that the content of one of six antigens in the auditory cortex correlated with the number of tone-shock combinations. The antigen was not found in the liver and its amount was higher in the brain stem, as compared to cerebral cortex and cerebellum. The results suggest that this antigen may be involved in the processes of memory build-up.

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In experiments on rats, the influence was studied of dalargin on the elaboration and preservation of various homogeneous and heterogeneous conditioned reflexes (CRs) elaborated in single and multiple pairings. The effect of dalargin on the processes of learning and memory was compared with the action of the peptide on the activity of hypothalamic neurones. Administration of dalargin delayed the elaboration of maze defensive CRs and practically did not affect the elaboration of two-way avoidance. The preservation of CR also deteriorated under the influence of dalargin. Administration of dalargin 10 min before the CRs testing did not prevent their reproduction. When using CRs elaborated in a single pairing, dalargin disturbed the preservation of the drinking CR and improved that of passive avoidance CR. Dalargin in this dose affected the emotional state of animals in the open field and did not significantly affect their motor activity. Dalargin suppressed impulse activity in 17 out of 22 tested neurones of the lateral hypothalamus, with maximum effect in 20-50 min after its administration. The obtained data show that the character of dalargin action on the elaboration of CR and mainly on its consolidation, depends on the character of the elaborated CR and is probably due to great extent to the effect of the peptide on the brain emotional mechanisms.

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In experiments on mice, the effect of cyclic analogue of enkephalin (CAE) on the processes of learning and memory was studied in control animals and in animals with changed functional state of monoaminergic brain systems. Administration of the peptide to intact animals significantly accelerated the acquisition of conditioned reflexes of two-way avoidance and did not significantly affect the retention of these reflexes and their subsequent reproduction. Retention and reproduction of conditioned reflexes elaborated in one combination, was disturbed. Administration of iprazid did not eliminate the "accelerating effect" of CAE on the formation of conditioned reflexes of the two-way avoidance but sharply disturbed their retention. In such conditions, the amnesing iprazid effect increased still more. Besides, under CAE effect, the activity of acetylcholinesterase in the motor and especially in the visual cortex of the mice increased. The obtained data testify to an important role of the monoaminergic and cholinergic brain mechanisms in realization of CAE effects on the processes of learning and memory.

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