Effects of MPEP on avoidance learning in rats.

In recent years metabotropic glutamate receptors (mGluRs) have received considerable attention as a potential target for psychotropic drugs, but their influence on learning and memory is still unclear. The aim of the present study was to examine whether intraperitoneal (i.p.) administration of selective mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyrydine (MPEP), injected prior to, immediately after or 30 min after training, affects acquisition and/or retrieval of the inhibitory step-down and active shuttle-box avoidance in rats. Our results indicate that 5 or 10 mg/kg i.p. MPEP in all tested groups impaired memory consolidation of step-down training without affecting acquisition and had no effect on learning and retention in shuttle-box trained rats. The data are in agreement with the statement that mGluR5s may contribute very little and task-dependently to the actual acquisition of new information, but memory formation, appears to require mGluR5s through modulation of consolidation and/or recall.

Effect of the calcium channel blockers nifedipine and diltiazem on pentylenetetrazole kindling-provoked amnesia in rats.

A large body of research supports the view that memory disturbance is an integral part of epilepsy. Deficit in various behaviour tasks has been found in rats subjected to experimental epilepsy-pentylenetetrazole (PTZ) kindling. In the present study we examined the effect of post-training administered calcium channel blockers nifedipine (10 and 40 mg/kg) and diltiazem (10 and 30 mg/kg) on amnesia induced by PTZ kindling in shuttle-box- and step-down-trained rats. Retention in nifedipine- or diltiazem-treated kindled animals was significantly improved compared to the kindled controls. The mechanisms of action of calcium antagonists studied is considered. Taken together with the data about calcium channel blocker anticonvulsive activity, the results of this study further suggest that nifedipine and diltiazem might be useful in the treatment of cognitive disorders in epileptic patients.

The GABA-B antagonist CGP 36742 prevent PTZ-kindling-provoked amnesia in rats.

Deficit in active and inhibitory avoidance behaviour has been found in pentylenetetrazole (PTZ)-kindled rats. This supports the view that memory deficit is an integral part of epilepsy. In the present study we examined the effect of the GABA B antagonist CGP 36742 on memory deficit induced by PTZ-kindling in shuttle-box- and step-down-trained rats. The retention in CGP 36742-treated animals was significantly improved compared to the kindled controls. The mechanisms of action of CGP 36742 is considered. The favourable effect of the GABA B antagonist in cases of amnesia provoked by PTZ-kindling might be of interest in clinical practice.

Effects of flunarizine and nitrendipine on electroconvulsive shock- and clonidine-induced amnesia.

This study was designed to examine the calcium channel blockers flunarizine and nitrendipine for their ability to prevent electroconvulsive shock (ECS)- or clonidine-induced deterioration of the inhibitory avoidance performance (step-down) in rats. Flunarizine (10 mg/kg) and nitrendipine (40 mg/kg) were found to prevent the ECS- or clonidine-provoked amnesia after oral administration for 12 days. The mechanisms of action of the two drugs are considered. The results of this study further suggest that calcium antagonists might be useful in the treatment of cognitive disorders.

Effects of verapamil on electroconvulsive shock- and clonidine-induced amnesia.

The effect of the Ca2+ blocker verapamil on amnesia induced by electroconvulsive shock (ECS) or by the alpha-adrenoceptor agonist clonidine was studied in male Wistar rats trained in passive avoidance task ("step down"). Clonidine (0.1 mg/kg, i.p.) and ECS induced a pronounced amnesia, significantly reducing the percentage of rats that had acquired the task upon retention tests, given 3 h, 24 h and 7 days after training. Verapamil (10 mg/kg) administered orally for 12 days (5 days before and 7 days after training) completely abolished the ECS- or clonidine-induced amnesia. These data suggest that calcium channel blocker verapamil has a protective effect against experimentally provoked memory deficit and might be useful for the treatment of cognitive disorders.

Effects of beta-adrenoceptor blocker pindolol, calcium antagonist verapamil and their combination on retention in step-down- and shuttle-box-trained rats and on brain biogenic monoamines.

The effects of the beta-adrenoceptor blocker pindolol and the calcium antagonist verapamil administered alone or in combination on retention in step-down- and shuttle-box-trained rats and on the biogenic monoamine levels in the frontal cortex and hippocampus were examined. The chronic oral treatment with pindolol impaired retention in step-down- and shuttle-box-trained rats, decreasing the dopamine (DA) and noradrenaline (NA) levels and increasing the serotonin (5-HT) levels in the cortex and hippocampus. Verapamil did not influence retention in step-down- and shuttle-box avoidance situation and the biogenic monoamine levels in the frontal cortex and hippocampus. It should, however, be noted that the chronic oral treatment with verapamil completely abolished the retention-impairing effect of pindolol, restoring to normal DA, NA and 5-HT levels. These findings might be of interest to clinical practice and suggest the necessity for using a combination of beta-blockers with Ca2+ antagonists in case of prolonged treatment of cardiovascular diseases.

Piracetam and fipexide prevent PTZ-kindling-provoked amnesia in rats.

Deficit in active and inhibitory avoidance behaviour has been pentylenetetrazole (PTZ)-kindled rats. This supports the view that memory deficit is an integral part of epilepsy. In the present study we examined the effect of the nootropic drugs piracetam and fipexide on memory deficit induced by PTZ-kindling in shuttle-box- and step-down-trained rats. The retention in piracetam- and fipexide-treated animals was significantly improved compared to the kindled controls. The mechanisms of action of the two drugs are considered. The favourable of nootropic drugs in cases of amnesia provoked by PTZ-kindling might be of interest in clinical practice.

Pentylenetetrazole kindling impairs long-term memory in rats.

The effect of pentylenetetrazole (PTZ) kindling on learning and retention in active (shuttle-box) and passive (step-down) avoidance was studied in rats. PTZ kindling did not impair learning and significantly disturbed long-term memory estimated from retention tests, i.e. PTZ kindling induced a retrograde amnesia in the active and passive avoidance situations. The present results support the view that memory deficit is an integral part of epilepsy.

The 5-HT2 receptor antagonist ketanserine prevents electroconvulsive shock- and clonidine-induced amnesia.

The 5-HT2-selective antagonist ketanserine was examined for its ability to prevent electroconvulsive shock (ECS)- or clonidine-induced performance deficit in the passive avoidance situation (step-down) in rats. The posttrain intraperitoneal injection of ketanserine at doses of 3 and 10 mg/kg prevented the ECS- or clonidine-provoked amnesia upon retention tests given 3 h, 24 h, and 7 days after training. The present data favor the view that the selective modification of 5-HT2 receptors after training can prevent the performance deficit in step-down-trained rats and suggest a role of the 5-HTergic neurotransmitter system in memory. The results of this study further suggest that 5-HTergic receptor antagonists might be useful in treatment of cognitive disorders.

Adafenoxate abolishes the amnesia induced by neonatal 6-hydroxydopamine treatment in rats.

The effect of neonatal 6-hydroxydopamine (6-OHDA) treatment on learning and memory and on the levels of biogenic monoamines in some brain structures, as well as the influence of the nootropic drug adafenoxate on 6-OHDA effect was studied in shuttle box and step down trained rats. In mature rats injected with 6-OHDA postnatal, learning and retention were impaired and the noradrenaline (NA) level in the frontal cortex and hippocampus was decreased. Adafenoxate abolished the amnestic effect of 6-OHDA and restored the NA level to normal in the above-mentioned brain structures. This finding suggests the important role of the noradrenergic neurotransmitter system in 6-OHDA-induced amnesia and the favorable effect of adafenoxate on learning and memory impaired by 6-OHDA.

Impairment of learning and memory in shuttle box-trained rats neonatally injected with 6-hydroxydopamine. Effects of nootropic drugs.

The effect of neonatal 6-hydroxydopamine (6-OHDA) treatment on learning and retention and on the level of biogenic monoamines in some brain structures as well as the influence of the nootropic drugs--piracetam, aniracetam, meclofenoxate and fipexide on the 6-OHDA-induced effect was studied. Two- way active avoidance (shuttle box) was used. The levels of noradrenaline (NA), dopamine (DA) and serotonin (5-HT) in the frontal cortex, striatum, hypothalamus, hippocampus and pons were measured. In mature rats, injected with 6-OHDA (100 mg/kg s.c.) in the first 3 postnatal days learning and retention were impaired and the NA level in the frontal cortex and hippocampus was decreased. Piracetam (600 mg/kg), aniracetam (50 mg/kg), meclofenoxate (100 mg/kg) and fipexide (10 mg/kg) administered orally 5 days before and 5 days during training, abolished the amnestic effect of 6-OHDA and restored to control values the NA level in the frontal cortex and hippocampus. This finding suggests the important role of the noradrenergic neurotransmitter system in the 6-OHDA-induced amnesia, as well as in the favorable effect of the nootropic drugs tested on 6-OHDA-impaired memory processes.

Memory impairment induced by combined disturbance of noradrenergic and dopaminergic neurotransmissions: effects of nootropic drugs.

The effect of the combined application of the alpha 2-adrenoreceptor agonist clonidine and of the dopaminergic blocker haloperidol on the memory processes was tested on albino rats. The changes in the memory were studied using the following methods: two-way active avoidance with negative reinforcement (shuttle-box) and passive avoidance (step-through). Both clonidine (0.05 mg/kg) and haloperidol (0.5 mg/kg), injected intraperitoneally immediately after the end of the training session, slightly impaired retention in the memory tests used with both training methods. Their combined application, however, caused a marked amnesia. This amnesia model was used to study the effects of the nootropic drugs: adafenoxate and the newly-synthesized compound benzoyl-1, 4-dipyrolydinone (p-P). Administered orally in a dose of 100 mg/kg for 5 days prior to the training session, both adafenoxate and p-P fully eliminate the amnesia caused by the combined application of clonidine and haloperidol. The paper discusses the role of the noradrenergic and dopaminergic neurotransmitter systems for the amnestic effect of the clonidine + haloperidol combination, as well as for the favourable effect on the cognitive functions of the tested nootropic drugs adafenoxate and p-p.

Learning and memory impairment in albino rats after potassium ethylxanthogenate. Effects of nootropic agents.

The effects of the nootropic agents piracetam, aniracetam, meclofenoxate and fipexide on the cognitive functions impaired after potassium ethylxanthogenate, inhibitor of dopamine-beta-hydroxylase, were tested in experiments on albino rats. The changes in learning and memory were traced by the active conditioned avoidance method with negative reinforcement (shuttle-box) and the passive avoidance method (step-down). Potassium ethylxanthogenate, injected intraperitoneally in a dose of 100 mg/kg, markedly impaired learning and memory with both methods used. Piracetam (600 mg/kg), aniracetam (50 mg/kg), meclofenoxate (100 mg/kg) and fipexide (10 mg/kg), administered orally five days before and five days during shuttle-box training, as well as five days before step-down training, completely prevented the impairing effect of potassium ethylxanthogenate on the cognitive processes. The role of the noradrenergic neurotransmitter system and of other brain transmitter systems for memory disturbances caused by potassium ethylxanthogenate, as well as the protective effect of the nootropic drugs used, are discussed.

Effect of diazepam and medazepam on pentylenetetrazol kindling in albino rats.

Experiments on male albino rats were carried out in order to study the effects of diazepam and medazepam on the clonic-tonic convulsions in kindling phenomena evoked by multiple injections of a subconvulsive dose (40 mg/kg) pentylenetetrazol (PTZ). In the two doses used, both diazepam (0.25 and 1.0 mg/kg) and medazepam (2.0 and 5.0 mg/kg) manifest a marked anticonvulsive effect on the clonic-tonic convulsions in PTZ-kindled rats, with a marked dose-effect dependence. The evidence in the literature that the hippocampus plays the role of a pathologically determining structure in the realization of the PTZ kindling and that neurotransmission in the inhibitory synapses in the hippocampus is achieved by gamma-aminobutyric acid (GABA), gives grounds to accept that the anticonvulsive effects of diazepam and medazepam, observed in PTZ kindling, occur through GABA-ergic mechanisms, because the facilitating effect of benzodiazepines on the GABA-ergic neurotransmission is well known.

Influence of nootropic drugs on the memory-impairing effect of clonidine in albino rats.

The effects of four nootropic drugs (piracetam, aniracetam, meclofenoxate and fipexide) on cognitive functions impaired by the antihypertensive drug clonidine were investigated in albino rats. The changes in learning and memory were studied by two-way active avoidance with punishment reinforcement (shuttle box). Clonidine injected intraperitoneally at a dose of 0.1 mg/kg immediately after a one-day shuttle box training significantly impaired retention. A 5-day treatment before the training session with piracetam 600 mg/kg, aniracetam 50 mg/kg, meclofenoxate 100 mg/kg and fipexide 10 mg/kg completely abolished the memory-impairing effect of clonidine. The role of the NAergic neurotransmitter system in the clonidine-induced disturbances of cognition, as well as in the protective effects of nootropic drugs, was discussed.