Effects of antipsychotic drugs on 5-HT2 receptors in the medial prefrontal cortex: microiontophoretic studies.
Microiontophoretic application (10-80 nA) of the relatively selective serotonin 2 (5-HT2) agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane [+/-)-DOI), suppressed medial prefrontal cortical (mPFc) cell's firing rate in a dose-dependent manner. This effect was antagonized by the antipsychotic drugs (APDs) clozapine (CLOZ) and spiperone (SPIP), with CLOZ displaying a greater potency in blocking DOI's action in the mPFc. In contrast, the typical APDs haloperidol (HAL) and L-sulpiride (SUL) failed to block DOI's effect. These results suggest that certain APDs interact with 5-HT2 receptors. Although 5-HT2 antagonism alone may not distinguish typical versus atypical APDs, it is possible that their 5-HT2/dopamine 2 (D2) binding ratio is important.
Ashby
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Department of Psychiatry and Behavioral Science, SUNY, Stony Brook 11794-8790.
Wang
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D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D003024:Clozapine / Q000494:pharmacology*; D003984:Dibenzazepines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005071:Evoked Potentials / Q000187:drug effects; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism*; D006220:Haloperidol / Q000494:pharmacology; D007478:Iontophoresis; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D013134:Spiperone / Q000494:pharmacology*
D000662:Amphetamines; D014150:Antipsychotic Agents; D003984:Dibenzazepines; D011985:Receptors, Serotonin; D013134:Spiperone; D003024:Clozapine; D006220:Haloperidol; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine