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.