RESUMO
RATIONALE: Ketamine is an NMDA receptor antagonist with psychotogenic and cognitive effects in healthy volunteers and schizophrenic patients which has been proposed to be a useful tool to investigate neurobiological basis of schizophrenia. OBJECTIVE: The present study characterized the effects of a subanesthetic dose of ketamine on memory and related subjective states of awareness in healthy volunteers. METHODS: Twenty-six subjects were given either a 60-min ketamine (0.5 mg/kg per hour) or a placebo infusion. To obtain constant plasma ketamine throughout the experiment, ketamine was administered using a computer-controlled infusion system. Subjects carried out episodic memory tasks involving words presented before and during infusion. Memory performance was assessed with recognition and free recall tasks. Subjective states of awareness were assessed using an experiential approach. Levels of psychopathology were evaluated with BPRS. RESULTS: Ketamine impaired performance in free recall and recognition of words presented during, but not before, infusion. There were no differences between groups concerning states of awareness associated with recognition memory. Subjects under ketamine had higher BPRS total scores as well as BPRS negative and positive cluster scores than control subjects. CONCLUSIONS: Ketamine decreases episodic memory performance by impairing encoding, but not retrieval processes. It does not selectively impair subjective states of awareness associated with recognition memory as it has been seen in patients with schizophrenia. Ketamine might mimic the memory impairment associated with acute, but not chronic, forms of schizophrenia.
Assuntos
Conscientização/efeitos dos fármacos , Antagonistas de Aminoácidos Excitatórios/farmacologia , Ketamina/farmacologia , Memória/efeitos dos fármacos , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Adulto , Atenção/efeitos dos fármacos , Feminino , Humanos , Ketamina/sangue , Masculino , Rememoração Mental/efeitos dos fármacosRESUMO
A paradigm based on conditioned suppression of ongoing motor activity, sensitive to latent inhibition (LI), was developed and tested in healthy volunteers. Subjects were trained to move disks from one peg to another with a high degree of regularity in the Tower of Toronto puzzle, a well-known cognitive skill learning task. Once this was achieved, they were submitted to a Pavlovian conditioning procedure. The conditioned stimulus (CS) was a pure tone and the unconditioned stimulus (US) a loud white noise. The resulting response suppression was assessed by a transient increase in latency of the hand movements. In control subjects, there was non-contingent CS and US presentation. The results evidenced conditioning after a single CS-US pairing. Following five preexposures to the to-be-conditioned CS, however, conditioning was abolished, seemingly expressing LI. Because a weak unconditioned response to the tone was observed after its first two presentations, an additional experiment was performed with two preexposures to the to-be-conditioned CS. With such procedure, conditioning was obtained, supporting the existence of LI in the preceding experiment. These results indicate that the present paradigm may be useful for the study of LI in human subjects, having the advantage of being similar to the experimental conditions used in the majority of LI studies in experimental animals.
Assuntos
Aprendizagem por Associação , Cognição , Condicionamento Clássico , Inibição Psicológica , Período Refratário Psicológico , Estimulação Acústica , Adulto , Feminino , Habituação Psicofisiológica , Humanos , Masculino , Modelos Psicológicos , Testes NeuropsicológicosRESUMO
The sensitivity of latent inhibition (LI) to amphetamine has been tested in humans with a paradigm close to the conditioned emotional response suppression currently used in experimental animals. The conditioned stimulus (CS) was a tone, the unconditioned stimulus (US) a strong white noise, and the response a transient delay in a regular sequence of hand movements in the resolution of the Tower of Toronto puzzle. The aim of this study was to verify whether the previously reported, disruptive effect of CS preexposure on conditioning really represents LI, by examining its sensitivity to amphetamine. Three groups of healthy volunteers received placebo, 5 or 10 mg of dexamphetamine sulphate, respectively, in a double-blind experimental design. The preexposure, conditioning and test phases were carried out under either amphetamine or placebo. The non preexposed groups treated with amphetamine were not different from the non preexposed placebo group, indicating that amphetamine did not affect conditioning. Among the preexposed groups, those receiving 10 mg of amphetamine showed normal rates of conditioning, whereas those treated with either 5 mg of amphetamine or placebo showed LI. Similar results have been reported in experimental animals. This sensitivity to amphetamine suggests that the present paradigm may be used to study LI in humans.