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Biomedical subjects

V M Getsova

Publications and source records attributed to V M Getsova.

At least 19 recordsLinked to original sources

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.

Animals↗

[Pharmacological reminder of the emotional condition facilitates the amnestic memory trace retrieval].

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.

Animals↗

[Changes in the content of water-soluble brain proteins-antigens during bilateral avoidance training of rats].

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.

Acoustic Stimulation↗

[Mechanisms of enkephalin action on learning and memory processes].

The influence of enkephalin on the processes of elaboration and preservation of the defensive conditioned reflexes of bilateral avoidance (CRBA) and conditioned reflexes of passive avoidance (CRPA) in intact rats and animals with changed functional state of serotoninergic system of the brain has been examined. Injection of enkephalin in dose of 10 mkg to intact animals accelerated the elaboration of CRBA not influencing in this case their preservation, but deeply disturbed the CRPA preservation. The excess of serotonin in the brain created by means of 5-oxytryptophan fully prevented the acceleration of CRBA elaboration by enkephalin under the usual conditions. Injection of enkephalin at the background of serotonin lowering and raising in the brain favoured CRBA preservation. Under the enkephalin influence the inclusion of [3H]tyrosine and [14C]lisine in water-soluble and water-insoluble proteins of different cerebral structures lowered. The obtained data testify to participation of serotoninergic system and brain proteins in the mechanisms of enkephalin action to the processes of learning and memory.

5-Hydroxytryptophan↗

[Comparison between changes in the concentration of nerve tissue specific and nonspecific proteins in several brain structures of rats during elaboration of a conditioned bilateral defense reflex].

Comparison of the time course of the content of brain-specific and brain-nonspecific proteins in five different structures of the central nervous system immediately and one or seven days after the conditioned reflex development has shown that functions of these proteins seem to be different. They are triggered at different stages of the conditioned reflex development irrespective of the fact that both proteins are likely to be implicated in the processes of information consolidation and storage.

Animals↗

Effect of serotonin on Y-maze retention and hippocampal protein synthesis in rats.

The effect of serotonin (5-HT) on consolidation of a brightness discrimination reaction was investigated in rats. Five microgram 5-HT, injected intrahippocampally immediately after training, impaired retention of the brightness discrimination tested 24 hr later. In biochemical experiments, leucine incorporation into hippocampal proteins in vivo was 32% inhibited by 5 microgram 5-HT. Leucine incorporation into proteins of hippocampal slices in vitro was decreased by 5 x 10(-5)M 5-HT. The results seem to support Essman's assumption that inhibition of brain protein synthesis by 5-HT may be responsible for the memory impairment. But also some other possibilities for a mechanism of 5-HT amnesia must be discussed.

Animals↗

Relationship between the peculiarities of elaboration and retention of brightness discrimination and the serotonin content in the rat brain.

The role of serotonin in memory consolidation was investigated by comparing the serotonin content in the brain of young and old animals which differed in the duration of consolidation process and by comparing the serotonin content in the brain with the efficiency of retrieval of memory traces in animals of the same age. Old rats had the serotonin content higher in the hippocampus and lower in the hemispheres, diencephalon, midbrain and medulla as compared with young ones. Elaboration of brightness discrimination increased the brain serotonin content in old animals and decreased it in young ones. Inverse correlation occurred between the serotonin content in the hippocampus, midbrain and the medulla and retention of conditioned reflexes in rats of the same age. No correlation occurred between the serotonin content in the cerebral structures and the rate of conditioning.

Age Factors↗

Content of norepinephrine and serotonin in symmetrical divisions of the brain of rats in the norm during learning and with the administration of peptides.

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.

Animals↗

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.

Amnesia↗

[The neurochemical mechanisms of the formation and consolidation of haloperidol-induced catalepsy].

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.

Animals↗

[Effect of an excess of serotonin in the brain on consolidation of temporary connections].

As a result of intravenous administration of 100 mg/kg of 5-oxytryptophane (5-OTP) to mice, the serotonin content in the brain rises in ten minutes by 35 to 37 per cent, and in an hour, by 58 to 60 per cent, and declines in a day to its initial level. In case of elaboration of passive avoidance reflexes (PAR) an hour after 5-OTP injection, their preservation considerably decreases in a day's time, while 5-OTP administration immediately following PARs elaboration does not affect their preservation. However, 5-OTP injected after PARs elaboration to animals subjected to preliminary cooling, sharply deteriorates their preservation. These facts in conjunction with the previously obtained date attest that excess of serotonin in the brain has a negative effect on the earliest stages of consolidation. When the animals are cooled and the brain temperature is reduced, the consolidation processes are retarded; as a result, the temporary connections prove to be still vulnerable to the action of serotonin excess set up after PAR elaboration.

5-Hydroxytryptophan↗