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.

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.

Influence of nootropic drugs on the memory-impairing effect of diethyldithiocarbamate and clonidine in "step down" passive avoidance in albino rats.

Experiments on albino rats were carried out to study the effects of the nootropic drugs piracetam, aniracetam, meclofenoxate and fipexide on the DA-beta-hydroxylase inhibitor diethyldithiocarbamate- and the alpha 2-adrenoceptor agonist clonidine-impaired cognitive functions. The changes in memory were studied by the step down passive avoidance with punishment reinforcement. Diethyldithiocarbamate, injected intraperitoneally at a dose of 300 mg/kg and clonidine at a dose of 0.1 mg/kg i. p. considerably impaired retention for passive avoidance. The administration of piracetam (600 mg/kg), aniracetam (50 mg/kg), meclofenoxate (100 mg/kg) and fipexide (10 mg/kg) orally for 5 days prior to training completely abolished the memory-impairing effect of diethyldithiocarbamate and clonidine. The role of NAergic neurotransmitter system for the memory disturbances caused by diethyldithiocarbamate and clonidine as well as for the protective effects of the nootropic agents tested is discussed.