Influence of eserine on the learning and memory facilitating effect of central stimulants.

In experiments with albino rats trained and tested for memory in a multi-chamber maze using various motor tasks it has been found that eserine in a dose of 0.50 mg/kg, applied 20 min before training, improves learning, whereas in doses of 0.30 and 0.50 mg/kg, applied before or immediately after training, it improves retention in the experimental animals. The central stimulants: caffeine 5 mg/kg, strychnine 1 mg/kg and amphetamine 1 mg/kg, administered i.p. before training, improve learning and retention. Caffeine (20 mg/kg), strychnine 1 mg/kg and amphetamine 1 mg/kg, applied after training, improve the retention of the experimental animals. The central stimulants, applied on the background of 0.10 mg/kg eserine before training or 0.30 mg/kg immediately after training, significantly potentiate their learning and/or memory-facilitating effect. It is assumed that eserine potentiates the positive effects of the stimulants on retention, activating moderately the cerebral cholinergic structures. This probably facilitates the interaction of the stimulants with the mechanisms regulating the memory processes.

Cholinergic mechanisms in the learning and memory facilitating effect of the central stimulants. II. Influence of anticholinergic agents on the learning and memory facilitating effect of strychnine.

In experiments involving training of albino rats in a maze it has been found that strychnine (1 mg/kg) introduced 5 min before or immediately after training, improves learning and retention. Upon blocking of the central muscarine-sensitive cholinergic structures (scopolamine 2 mg/kg) and of the nicotine-sensitive structures (spasmolytin 20 mg/kg), the learning and memory facilitating effect of strychnine is not manifested. The realization of the learning and memory facilitating effect of strychnine requires optimum functional level of the activity of the central cholinergic system.

Cholinergic mechanisms in the learning and memory facilitating effect of the central stimulants. III. Influence of the anticholinergic agents on the learning and memory facilitating effect of amphetamine.

In experiments involving training of albino rats in a maze it has been established that amphetamine in a dose of 0.5 mg/kg introduced 15 min before learning has almost no effect, in a dose of 2 mg/kg it slightly deteriorates learning and retention, while in a dose of 1 mg/kg both learning and retention are markedly improved. However, introduced immediately after training, all three doses tested improve retention upon testing 24 hours and 14 days after training. Upon blocking of the central muscarine-sensitive cholinergic structures (scopolamine 2 mg/kg) and of the nicotine-sensitive structures (spasmolytin 20 mg/kg), the learning and memory facilitating effect of amphetamine is not manifested in the two experimental setups (introduction before and after training). The results resemble the case of independent administration of cholinolytics only, i.e. complete blocking of learning and memory induced by scopolamine and considerable deterioration induced by spasmolytin. The results obtained show that the realization of the learning and retention facilitating effect of amphetamine requires optimum functional level of the activity of the central cholinergic system.

On certain effects of dopaminergic agents in pentylenetetrazol convulsions.

In experiments with pentylenetetrazol convulsion model it has been found that L-DOPA in a dose of 50 mg/kg has no influence, while 500 mg/kg potentiate convulsions. Amantadine in a dose of 25 mg/kg and particularly markedly in a dose of 100 mg/kg potentaites convulsive seizures. Amphetamine in a dose of 0.5 mg/kg has no effect, while 5 mg/kg potentiate convulsive seizures, which is particularly pronounced in mice. Apomorphine in doses of 0.5 and 5 mg/kg has no marked effect on convulsions. Haloperidol in doses of 0.2 and 2 mg/kg does not have a pronounced effect on convulsive-seizure reactions and does not influence the effect of L-DOPA and amantadine on these reactions. The results obtained suggested a rather indirect effect of the dopaminergic system on convulsive-seizure reactivity. It is possible that the effects of some of the dopaminergic agents studied are realized through influencing the relationships between the dopaminergic system and other neurotransmitter systems (especially cholinergic, GABA-ergic and serotonin-ergic).

Effect of methionine on the brain biogenic monoamines and on the cortical bioelectrical activity of rabbits.

Methionine (150 and 300 mg/kg ip for 3 days) did not change the concentrations of striatal DA. It was also without effect on the levels of NA and 5-HT in the diencephalon and in the brain stem, while the 5-HIAA content was significantly increased in both structures after the dose 300 mg/kg. The single injection of methionine in doses of 10--300 mg/kg iv provoked dose-dependent changes in cortical bioelectrical activity. It was observed a considerable increase in the number of spindles, an increase in the amplitude and number of waves composing the spindles as well as a rise in their frequency characteristic.

Experimental study of the effects of imidazol, papaverine and histamine on convulsive-seizure reactivity.

In experiments on male albino rats and mice a study is made of the effects of imidazol which is a phosphodiesterase stimulator, papaverine which inhibits phosphodiesterase and histamine which stimulates adenylate cyclase, on the convulsive-seizure reactivity. The substances are introduced intraventricularly and intracerebroventricularly, imidazol also intraperitoneally in different doses and at different intervals before the convulsive agent. Electrical, pentylenetetrazol (Cor) and strychnine convulsion models are used. The effect of imidazol on the spontaneous cortical bioelectrical activity is studied throuth its i. v. administration in rabbits. Imidazol markedly increases the convulsive reactivity, and in large doses it alone results in electrographic and motor convulsions. Paperine slightly lowers the convulsive-seizure reactivity only in pentylenetetrazol convulsions. The results obtained and their comparison with the results of previous experiments of ours with other drugs affecting the cyclic adenosinemonophosphate (cAMP) system, such as lithium, haloperidol, caffeine and theophyline, do not permit to assume a considerable significance of the influence of these substances (in the doses tested) on the cAMP system in the mechanisms of their effects on the convulsive-seizure reactivity.

On certain relationships between gamma-aminobutyric acid (GABA) and adrenergic mechanisms in convulsive-seizure reaction.

In experiments on male albino mice it has been established that upon intracerebroventricular administration in doses of 50, 100 and 300 mug per mouse GABA markedly inhibits the convulsive-seizure reactions in pentylenetetrazol and electroconvulsions and has no substantial effect on strychnine convulsions (the dose of 300 mug is toxic). Diethyldithiocarbamate (DDC) in a dose of 400 mg/kg, introduced i.p. 3 hours in advance, increases the convulsive reactivity in pentylenetetrazol and electroconvulsions. On the background of DDC the inhibitory effect of GABA is expressed only in antagonizing of the DDC effect increasing the convulsive reactivity. Alpha-methyl-paratyrosine (a-MT) in a dose of 250 mg/kg, introduced i.p. 4 hours in advance, has no substantial effect on the convulsive reactivity. On the background of alpha-MT the inhibitory effect of GABA in electroconvulsions does not change essentially, however, in pentylenetetrazol convulsions the GABA effect is practically not manifested. The results obtained show that the changes in the correlations between the catecholamines and GABA in the central nervous system result in substantial changes in the convulsive-seizure reactivity. The lower catecholamines level does not permit the marked manifestation of the GABA inhibitory effect. However, GABA counteracts to a certain extent the rise in the convulsive reactivity as a result of the drop in the brain level of the catecholamines.

Cholinergic mechanisms in the learning and memory facilitating effect of caffeine.

Experiments are made to train rats in a maze involving memory tests 24 hours and 14 days after training. As it was established in previous studies of the authors, caffeine introduced in low doses (5 mg/kg) 5 min before training facilitates learning and memory. Applied immediately after training, caffeine even in higher doses (20 mg/kg) also improves the memory indices 24 hours and 14 days after the experiment. The anticholinergic agents spasmolytine and scopolamine in higher doses (20 and 2 mg/kg respectively) have a markedly deteriorating effect on learning, while scopolamine deteriorates retention as well. Introduced after training, both drugs deteriorate memory even in smaller doses - 2 and 0,25 mg/kg, respectively. On the background of the anticholinergic agents (especially in the higher doses), the learning and memory facilitating effects of caffeine are not manifested in any of the experimental setups (administration before and after train. The results obtained show that cholinergic mechanisms play an important role in the learning and memory facilitating effect of caffeine. A necessary condition for the manifestation of this effect is the optimum functional level of these cholinergic mechanisms in the central nervous system.

The influence of methionine on rats and mice behaviour.

Methionine given ivc or ip to rats and ic to mice acts only slightly on the central nervous system of these animals; it has either stimulating or inhibiting action, depending on the test applied.

Comparative studies on the effect of lithium and haloperidol on learning and memory.

A comparative study of the effect of lithium and haloperidol on the processes of learning and memory is carried out in experiments for training albino rats in a maze. Haloperidol introduced intraperitoneally 1 h before learning in a dose of 0.2 mg/kg deteriorates the learning and long-term memory, while a dose of 2 mg/kg makes these processes impossible. Introduced immediately after learning, haloperidol shows a tendency towards deterioration in the phase of memory consolidation. When administered 1 h before the long-term memory test, haloperidol inhibits reproduction. Lithium chloride administered in a single dose of 200 or 300 mg/kg before and after learning, has no pronounced effect. A tendency towards impairment of learning and memory is manifested only upon administration of doses of 200 mg/kg for 8 days in succession. The differences in the effects of lithium and haloperidol on learning and memory do not support the assumption that their similar effect on the cAMP system (inhibition of the adenylate cyclase in the brain) is essential for the mechanism of their effect on the central nervous system.