Effect of sertindole on extracellular dopamine, acetylcholine, and glutamate in the medial prefrontal cortex of conscious rats: a comparison with risperidone and exploration of mechanisms involved

Psychopharmacology
Arne MørkJ Arnt

Abstract

Second-generation antipsychotics have some beneficial effect on cognition. Recent studies, furthermore, indicate differential effects of second-generation antipsychotics on impairment in executive cognitive function. We evaluated the effect of the second-generation antipsychotic drug, sertindole, on extracellular levels of dopamine (DA), acetylcholine (ACh), and glutamate (Glu) in the rat medial prefrontal cortex (mPFC). Risperidone was studied for comparison. Moreover, selective serotonin 5-HT(2A), 5-HT(2C), and 5-HT(6) receptor antagonists were used, given alone and in combination with the preferential DA D(2) receptor antagonist, haloperidol, to further clarify the action of the two drugs. Rats were treated acutely with vehicle or drugs, and extracellular levels of neurotransmitters were assessed by microdialysis in freely moving animals. Sertindole and risperidone significantly increased extracellular levels of DA. Haloperidol; the 5-HT(2A) receptor antagonist, M100907; the 5-HT(2C) receptor antagonist, SB242084; and the 5-HT(6) receptor antagonist, GSK-742457, induced minor increases in levels of DA, but the three latter compounds raised the DA levels notably in combination with haloperidol. Sertindole and risperidone sign...Continue Reading

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Related Concepts

Hepatitis D Infection
Serotonin 6 receptor
Antipsychotic Effect
Receptor, Serotonin,5-HT2A
Assay OF Haloperidol
Prefrontal Cortex
Extracellular
Serotonin Measurement
Serotonin
Antagonist Muscle Action

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