Subchronic treatment with either clozapine, olanzapine or haloperidol produces a hyposensitive response of the rat cortical cells to N-methyl-d-aspartate

Sep 21, 2000Neuroscience

Short-term treatment with clozapine, olanzapine, or haloperidol reduces sensitivity of rat brain cells to NMDA

AI simplified

Psychedelic Science on OpenScience ↗PubMed ↗DOI ↗

Abstract

Repeated administration of the antipsychotic drug haloperidol significantly hyperpolarized the resting membrane potential in pyramidal cells of the rat medial prefrontal cortex.

Clozapine and olanzapine, along with haloperidol, shifted the N-methyl-D-aspartic acid concentration-response curves to the right after subchronic treatment.
The ability of antipsychotic drugs to enhance N-methyl-D-aspartic acid-induced inward currents in pyramidal cells was significantly reduced following repeated exposure.
Haloperidol alone caused a significant increase in membrane resistance in pyramidal cells, unlike clozapine or olanzapine.
Subchronic treatment with haloperidol depressed responses induced by another compound, (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid.
The desensitization to N-methyl-D-aspartic acid may be a compensatory response to the effects of antipsychotic drugs on glutamate receptors.

AI simplified

Using the technique of intracellular recording in in vitro brain slice preparations, we examined the effects produced by repeated administration of the antipsychotic drugs clozapine, olanzapine and haloperidol, on N-methyl-D-aspartic acid-induced responses in pyramidal cells of the rat medial prefrontal cortex. Rats were anesthetized and decapitated 24h after the conclusion of daily intraperitoneal injection with either clozapine (25mg/kg), olanzapine (1, 5 or 10mg/kg) or haloperidol (0.5mg/kg) for 21 days, and the slices from medial prefrontal cortex were used for electrophysiological recordings. The concentration-response curves for N-methyl-D-aspartic acid to activate cortical cells shifted markedly to the right in rats which received the subchronic antipsychotic drug treatment, compared with those obtained from rats which received repeated injections of vehicle (1ml/kg/day, i.p. for 21 days). In addition, repeated exposure to antipsychotic drugs caused a significant reduction in the ability of these antipsychotic drugs to augment the N-methyl-D-aspartic acid-induced inward current in pyramidal cells of the rat medial prefrontal cortex. Repeated administration of haloperidol, but not clozapine or olanzapine, significantly hyperpolarized the resting membrane potential and increased membrane resistance in pyramidal cells of the medial prefrontal cortex. Moreover, subchronic treatment with haloperidol, but not clozapine or olanzapine, depressed (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid-induced responses. The desensitized response of medial prefrontal cortex cells to N-methyl-D-aspartic acid could be the result of a compensatory response to the facilitating action of antipsychotic drugs on N-methyl-D-aspartic acid receptor-mediated transmission. The inhibitory action of haloperidol on (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid responses may also contribute to the rightward shift of the N-methyl-D-aspartic acid concentration-response curve.Thus, the present study suggests that the atypical antipsychotic drugs, clozapine and olanzapine, as well as the typical antipsychotic drug haloperidol strongly modulate glutamatergic transmission after prolonged treatment. This might be an important factor in the mechanisms by which these drugs alleviate symptoms in schizophrenic patients.

Full Text

Full text is available at the source.

View full text (XML) ↗View full text ↗

Subchronic treatment with either clozapine, olanzapine or haloperidol produces a hyposensitive response of the rat cortical cells to N-methyl-d-aspartate

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the psychedelic science brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the psychedelic science brief