Dose-related effects of memantine on a mismatch negativity-like response in anesthetized rats.

Memantine is a low-affinity NMDA receptor antagonist that is used in the treatment of Alzheimer's disease to alleviate the cognitive symptoms of the disease. In humans, memantine has been shown to facilitate auditory change detection as reflected in the mismatch negativity (MMN) response recorded in the frontal cortex. In the present study we investigated the effects of memantine on the auditory MMN-like responses recorded in anesthetized rats. Saline, a low (3 mg/kg) or a high (10 mg/kg) dose of memantine was i.p. injected into the animals. Auditory MMN-like responses were recorded during the presentation of a repeated tone of one frequency (standard, P=0.956) that was rarely replaced by a tone of another frequency (deviant, P=0.044). The low dose of memantine did not observably affect the amplitude of the auditory MMN-like response, but it prolonged the duration of the response relative to saline. The high dose of memantine, in contrast, blocked the generation of the auditory MMN-like response. The findings suggest that memantine may, with appropriate doses, facilitate already this early stage of auditory processing.

[Characteristic features of adaptation to experimental conditions in primates with various initial keeping conditions]. / Osobennosti adaptatsii k éksperimental'nym usloviiam u primatov s razlichnymi iskhodnymi sposobami soderzhaniia.

Ethological study of emotional state and behavior was carried out in male macaques of two species (Macaca mulatta and Macaca fascicularis), which were divided in three groups according to their initial keeping: isolated, family, and gregarious. During instrumental conditioning, the initial keeping was changed for identical conditions (individual caging or sitting in a primatological chair). It was shown that adaptation to stress associated with a sharp enviromental change depended on initial keeping conditions. Monkeys brought up in family with experience of both intra- and interspecies interactions (for example, monkey--human) had the highest adaptation and learning abilities. Individual and gregarious keeping of monkeys impoverished their individual experience, and their adaptation to experimental conditions required additional efforts. The learning of individually caged monkeys was successful, if their keeping conditions were not changed. Initially gregarious monkeys were successfully trained after their habituation to contact with humans.

Involvement of the parafascicular nucleus of the thalamus and the cholinoreactive system of the neostriatum in controlling a food-procuring reflex in rats at different stages of learning.

A model of a Skinner box food-procuring reflex in rats was used to study the relationship between the strength applied to a pedal and disruption of the parafascicular nucleus of the thalamus and microinjections of the cholinolytic scopolamine and the cholinomimetic carbachol into the neostriatum at different stages of learning. In untrained rats at the stage of learning to press strongly on the pedal without the conditioned signal being switched on (i.e., every strong press was rewarded) showed (a) a decrease in the rate of learning to press strongly and an increase in the number of weak pedal presses after bilateral lesioning of the parafascicular nucleus of the thalamus; (b) that rats with bilateral lesions of this nucleus responded to microinjections of scopolamine into the neostriatum with increases in the number of strong presses, with no change in the number of weak pedal presses, while microinjections of carbachol decreased the number of strong and increased the number of weak presses as compared with the pre-microinjection baseline. In trained rats at the stage of recovery the reflex (i.e., strong pedal presses were reinforced only during exposure to the conditioned signal), lesioning of the parafascicular nucleus of the thalamus had the effect that the time required for recovery of the reflex became dependent on the level of pre-operative training; scopolamine microinjections into the neostriatum of rats achieving high levels of correct performances of the reflex only after surgery led to sharp degradation in performance of the reflex on the day of microinjections; microinjection of carbachol into the neostriatum of rats with low post-operative levels of performance of the reflex had no effect on this measure.

[The participation of the parafascicular thalamic nucleus and of the neostriatal cholinoreactive system in regulating the food-procuring reflex in rats at different stages of learning]. / Uchastie parafastsikuliarnogo iadra talamusa i kholinoreaktivnoi sistemy neostriatuma v reguliatsii pishchedobyvatel'nogo refleksa u krys na raznykh étapakh obucheniia.

Effects of bilateral lesions of the thalamic parafascicular nucleus (Pf) and bilateral microinjections of scopolamine (cholinolytic) and carbacholine (cholinomimetic) into rat neostriatum on the strength of pressing the bar at different stages of acquisition of food-procuring reflex were studied in 51 rats. At the stage of training of food-procuring movements (only strong bar pressings were reinforced) without introduction of a conditioned stimulus, the Pf lesions decreased the rate of learning and increased the number of week pressings. At this stage, scopolamine neostriatal microinjections against the background of the Pf lesions increased the number of strong and did not affect the number of week bar pressings. On the contrary, carbacholine decreased the number of strong and increased the number of week pressings in comparison with the preinjection background. In the trained group of rats, at the stage of reflex restoration (strong bar pressings were reinforced only during the action of a conditioned stimulus) after the Pf destruction, the reflex restoration time depended on the level of presurgery training. Striatal scopolamine injections that primarily after surgery led to a high level of correct reflex realization induced a sharp impairment in reflex performance on a microinjection day, and carbacholine microinjections against the background of low reflex performance did not change this level after surgery.

Effects of microinjection of scopolamine into the neostriatum of rats on performance of a food conditioned reflex at different levels of fixation.

Chronic experiments performed on 32 Sprague-Dawley rats using a movement-feeding operant reflex (Skinner box) model showed that microinjection of scopolamine into the neostriatum had effects on this reflex which depended on the stage of learning. In animals with weakly fixed reflexes (prior to reaching the stage of memory consolidation), bilateral microinjection of 0.3 microgram of scopolamine into the caudate nucleus completely inhibited the reflex for a prolonged period of time. When the operant habit was well fixed, bilateral microinjection of the same doses of scopolamine into the neostriatum had no effect on the reflex. These results suggest that the neostriatum cholinergic system is critically involved in forming the motor engram. The cholinergic system of the caudate nucleus either takes no part in realizing the well-fixed conditioned reflex movement response and/or other forebrain structures are involved in the reflex, compensating for the disturbance in neostriatal cholinergic function.

[Characteristics of the effect of microinjections of scopolamine into the rat neostriatum on the realization of a conditioned food reflex with different degrees of reinforcement]. / Osobennosti vliianiia mikroin' 'ektsii skopolamina v neostriatum krys na realizatsiiu pishchevogo uslovnogo refleksa raznoi stepeni uprochennosti.

In chronic experiments in 32 male Sprague-Dawley rats on the model of food instrumental reflex (Skinner box) it was shown that the effect of Neostriatal scopolamine microinjections (0.3 mkg) depended on the stage of reflex consolidation. Before the complete reflex consolidation the bilateral microinjections of scopolamine into Nucleus Caudatus produce prolonged inhibition of instrumental reflex. Bilateral Neostriatal microinjections of scopolamine in the same doze had no effect in the case of full consolidation of instrumental reflex. Our results suggest that the cholinergic Neostriatal system is crucially involved in the forming of motor engram of instrumental reaction. In the same time the cholinergic neostriatal system either is not involved in the execution of full consolidate instrumental reactions, or another different forebrain structures patricipate in their realization compensating disturbances of striatal cholinergic function.