RESUMO
The gamma aminobutyric acid-A (GABA-sub(A)) agonist, muscimol, the glutamate N-methyl-D-aspartate (NMDA) receptor antagonist, D-2-amino-5-phosphonopentanoic acid (AP5), and the inhibitor of the extracellularly regulated kinases (ERKs), UO 126, cause retrograde amnesia when administered to the hippocampus. In the present study, the authors found that they all cause retrograde amnesia for 1-trial inhibitory avoidance, not only when infused into the dorsal CA1 region of the hippocampus, but also when infused into the basolateral amygdala or the entorhinal, parietal, and posterior cingulate cortices. The posttraining time course of the effect of each drug was, however, quite different across brain structures. Thus, in all of them, NMDA receptors and the ERK pathway are indispensable for memory consolidation, and GABA-sub(A) receptor activation inhibits memory consolidation: but in each case, their influence is interwoven differently.
Assuntos
Amnésia Retrógrada/induzido quimicamente , Encéfalo/efeitos dos fármacos , Muscimol/efeitos adversos , Valina/análogos & derivados , Valina/efeitos adversos , Amnésia Retrógrada/fisiopatologia , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Comportamento Animal , Encéfalo/anatomia & histologia , Butadienos/efeitos adversos , Inibidores Enzimáticos/efeitos adversos , Agonistas GABAérgicos/efeitos adversos , Masculino , Inibição Neural/efeitos dos fármacos , Nitrilas/efeitos adversos , Ratos , Ratos Wistar , Tempo de Reação/efeitos dos fármacos , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Fatores de TempoRESUMO
RATIONALE: There is a dearth of studies which have employed sophisticated paradigms to investigate the effects of zolpidem on memory. OBJECTIVES: To explore anterograde cognitive deficits induced by acute oral doses of zolpidem by means of the process-dissociation procedure (PDP). METHODS: The present study followed a placebo-controlled, double-blind, parallel-group design. Young, healthy females were randomly allocated to one of three treatments with 12 subjects each: placebo, 5 mg and 10 mg zolpidem. Two word-stem completion tasks were carried out close to theoretical peak-plasma concentration: a) direct inclusion task with cued recall, in which participants had to try to use words seen at study to complete stems; and b) direct exclusion task, in which words seen at study were to be avoided as completions. The PDP was applied to the results in these tasks to yield indices of explicit/controlled (C) and implicit/automatic (A) memory. Classical psychometric tests were also carried out. RESULTS: Zolpidem 10 mg led to cognitive effects similar to benzodiazepines (except for the atypical lorazepam), including impairment of exclusion, but not inclusion-task performance. Results of the application of the PDP were inconclusive but concurred with the pattern established in previously published work on benzodiazepine effects, i.e. that zolpidem (10 mg) impaired C. CONCLUSIONS: Zolpidem leads to cognitive effects similar to most benzodiazepines. Although the application of PDP in drug studies may be counterproductive in view of methodological difficulties that are discussed, the pattern of effects on the stem-completion tasks involved in this paradigm is potentially useful in the investigation of cognitive effects of psychoactive drugs.