RESUMEN
Male CBA/Ca inbred mice were treated with a dose of 8 micrograms 2-mercapto-ethanol per animal per day in the drinking water from the age of 5 months onwards up to the age of 24 months. Dopamine release was greatly decreased in old animals in contrast to the elevation of dopamine release in the treated mice. Similarly, an elevated malondialdehyde content in brain homogenates was also observed in the aged treated animals compared with their controls. No essential differences were observed in locomotor activity and learning between treated an control mice.
Asunto(s)
Envejecimiento/metabolismo , Química Encefálica/efectos de los fármacos , Encéfalo/metabolismo , Dopamina/metabolismo , Malondialdehído/metabolismo , Mercaptoetanol/farmacología , Animales , Conducta Animal , Encéfalo/efectos de los fármacos , Antagonistas de Dopamina , Peroxidación de Lípido/efectos de los fármacos , Masculino , Malondialdehído/antagonistas & inhibidores , Ratones , Ratones Endogámicos CBARESUMEN
2-Mercaptoethanol (2-ME) has a beneficial effect on the mean life span of laboratory rodents. This paper deals with the effects of 2-ME on changes of dopamine release from brain slices of old aged or hypoxia exposed mice and rats. The results were compared with data which reflect spontaneous peroxidation of brain lipid constituents. In addition, adequate behavioural properties were studied. Long-term 2-ME treatment for months abolishes the age-related decrease of transmitter release and prevents changes in malondialdehyde formation. If age-dependent release failure is already established, then neither single high doses of 2-ME nor repeated treatment for 3 weeks are effective. Posthypoxic release inhibition is prevented by a 2-ME pretreatment for 3 weeks but not by an acute single application even at high dosages. The preventive effect of 2-ME is a mediated one rather than an immediate direct action. Age-related behavioural deficits, such as locomotor activity, habituation performance and learning ability, do not reflect any effect of 2-ME long-term treatment.
Asunto(s)
Envejecimiento , Encéfalo/metabolismo , Dopamina/metabolismo , Mercaptoetanol/farmacología , Animales , Conducta Animal/efectos de los fármacos , Peroxidación de Lípido , Masculino , Malondialdehído/metabolismo , Ratones , Ratones Endogámicos/psicología , Oxígeno/metabolismo , Ratas , Ratas EndogámicasRESUMEN
The effect of three anticonvulsants on several test methods for evaluation of memory-enhancing drugs have been studied in rats and mice. The results were compared to the results obtained from the nootropic piracetam and from imipramine. In an active avoidance test (pole jumping), repeated administration of carbamazepine (5 mg/kg i.p.) and piracetam (300 mg/kg p.o.) protected against impairment of learning rate caused by repeated application of an electroconvulsive shock. Valproate calcium (repeated administration of 30 mg/kg i.p.) was only weakly active, while clonazepam (repeated administration of 0.3 mg/kg i.p.) decreased the learning rate even more. Drugs were given in dosages which have no anticonvulsive activity in this test. The impairment of learning rate caused by repeated application of ethanol was prevented by carbamazepine (5 mg/kg i.p.), valproate calcium (30 and 100 mg/kg i.p.) and piracetam (100 mg/kg i.p.). Clonazepam (0.3 and 1 mg/kg i.p.) had a worsening effect on learning rate. In Porsolt's behavioral despair test, carbamazepine (5, 10 and 30 mg/kg i.p.) and valproate calcium (30 and 100 mg/kg i.p.) shortened the duration of immobility, which indicates an increased psychomotor activity. Clonazepam was ineffective. Results obtained with carbamazepine are similar to those obtained with piracetam. The data are discussed in view of the so-called psychotropic effects of carbamazepine in clinical trials.
Asunto(s)
Conducta Animal/efectos de los fármacos , Carbamazepina/farmacología , Clonazepam/farmacología , Memoria/efectos de los fármacos , Piracetam/farmacología , Pirrolidinonas/farmacología , Ácido Valproico/farmacología , Animales , Reacción de Prevención/efectos de los fármacos , Electrochoque , Etanol/farmacología , Masculino , Ratas , Ratas EndogámicasRESUMEN
AWD 23-15 (6-Methyl-1,2,3,4-tetrahydro-pyrimidin-2,4 dion) which is known to improve learning and memory processes in laboratory animals, was investigated in several hypoxia models. The following results were obtained: 1. Increase of survival rate, 2. change in hypoxia-induced decrease of cerebral post-mortem adenylic energy charge and in concentrations of metabolic products in the brain and 3. antagonism of the hypoxia-induced decrease of dopamine release. However in the general behavioral test the drug was ineffective. These results support the idea that AWD 23-15 is a potential nootropic drug.