Effects of caffeine on learning and memory in rats tested in the Morris water maze

We studied some of the characteristics of the improving effect of the non-specific adenosine receptor antagonist, caffeine, using an animal model of learning and memory. Groups of 12 adult male Wistar rats receiving caffeine (0.3-30 mg/kg, ip, in 0.1 ml/100 g body weight) administered 30 min before training, immediately after training, or 30 min before the test session were tested in the spatial version of the Morris water maze task. Post-training administration of caffeine improved memory retention at the doses of 0.3-10 mg/kg (the rats swam up to 600 cm less to find the platform in the test session, P<=0.05) but not at the dose of 30 mg/kg. Pre-test caffeine administration also caused a small increase in memory retrieval (the escape path of the rats was up to 500 cm shorter, P<=0.05). In contrast, pre-training caffeine administration did not alter the performance of the animals either in the training or in the test session. These data provide evidence that caffeine improves memory retention but not memory acquisition, explaining some discrepancies among reports in the literature

O extrato etanólico da planta tóxica brasileira, Psedocalymma elegans apresenta efeitos estimulantes sobre o sistema nervoso central / The central nervous system stimulant effects of the ethanolic extract from the toxic Brazilian plant Pseudocalymma elegans

Os efeitos do extrato etanólico da planta tóxica Pseudocalymma elegans (Vell.) Kuhlm. sobre o comportamento de camundongos foi estudado. Camundongos que receberam injeçöes intraperitoneais (i.p.), nas doses de 1.6 a 3g/kg de peso corporal, apresentaram convulsöes e morreram com uma latência média de 8 min. A LD50 foi estimada em 1.8g/kg. Os camundongos que receberam 1g/kg (i.p.) do extrato apresentaram um maior número de "rearings" e um maior tempo de "freezing" do que o grupo controle, quando observados em um campo aberto 30 min após a injeçäo. Durante o tempo em que esses animais foram observados no campo aberto näo ocorreram alteraçöes significativas no número de cruzamentos, tempo de "grooming" e número de bolos fecais. Quando esses animais foram colocados em um labirinto em cruz elevado exploraram menos os braços abertos do labirinto que os animais controle: apresentaram uma menor porcentagem de entradas e uma menor porcentagem de tempo de permanência nos braços abertos do labirinto. Esses animais apresentaram também uma menor atividade locomotora medida de forma automatizada e nenhuma alteraçäo no tônus muscular, avaliado pelo tempo de permanência em um arame esticado. Os três primeiros testes sugerem que a administraçäo de doses moderadas do extrato desencadeia um efeito "ansiogênico" contrário ao observado com a administraçäo de ansiolíticos depressores do sistema nervoso central (SNC). Doses maiores do extrato provocam uma super-estimulaçäo do SNC com convulsöes que, eventualmente, podem contribuir para a letalidade do extrato

Memory modulation by brain benzodiazepines

1. Recent evidence indicates that post-training memory processes are down-regulated by benzodiazepine/GABA-A systems inthe amygdala, septum and hippocampus. Havituation and avoidance learning are accompanied by a decrease of benzodiazepine-like immunoreactivity in the three structures, explainable by a release of benzodiazepines. Immediate post-training microinjection of the benzodiazepine antagonist flumazenil into the hippocampus enhances retention of habituation. The post-training administration of glumazenil into any of the three structures enhances relation of avoidance learning. 2. The mode of operation of these systems was studied in detail in the amygdala using avoidance paradigms. The release of endogenous benzodiazepines during and particularly after training enhances sensitivity of local GABA-A receptors to muscimol, activation of the GABA-A receptors opens chloride channels that can be selectively blocked by picrotoxin and by Ro-4864. Training enhances, and fluazenil reduces, sensitivity of the amygdala to the amnestic effect of locally injected muscimol by a factor of 100. Post-training intra-amygdala administration of picrotoxin or Ro5-4864 enhances retention. 3. These findings suggest that the endogenous benzoidiazepine/GABA-A mechanisms that down-regulate memory int he amygdala, septum and hippocampus are activated in response to the anxiety and/or stress associated with each task. Memory lability which occurs in the psot-training period and characterizes consolidation would thus be a consequence of the brain's response to anxiety or stress

Benzodiazepine receptor ligand influences on learning: an endogenous modulatory mechanism mediated by benzodiazepines possibly of alimentary origin

In rats pre-but not post-training ip administration of either flumazenil, a central benzodiazepine (BSD) receptor antagonist, or of n-butyl-B-carboline-carboxylate (BCCB), an inverse agonist, enhanced retention of inhibitory avoidance learning. Flumazenil vlocked the enhancing effect of BCCB, and the inhibitory effect of the BZD agonists clonazepam and diazepam also given pre-training. Post-training administration of these drugs had no effects. The peripheral BZD receptor agonist/chloride channel blocker Ro5-4864 had no effect on the inhibitory avoidance task when given ip prior to training, buth it caused enhancement when given immediately post-training either ip or icv. This effect was blocked by PK11195, a competitive antagonist of Ro5-4864. These results suggest that ther is an endogenous mechanism mediated by BZD agonists, which is sensitive to inverse agonists and that normally down-regulates the formation of memories through a mechanism involving GABA-A receptors and the corresponding chloride channels. The most likely agonists for the endogenous mechanism suggested are the diazepam-like BZDs found in brain whose origin is possibly alimentary. Levels of these BZDs in the cortex were found to sharply decrease after inhibitory acoidance training or mere exposure to the training apparatus.