5‐HT2A and D2 receptor blockade increases cortical DA release via 5‐HT1A receptor activation: a possible mechanism of atypical antipsychotic‐induced cortical dopamine release

摘要: Atypical antipsychotic drugs (APDs), all of which are relatively more potent as serotonin (5-HT)(2A) than dopamine D(2) antagonists, may improve negative symptoms and cognitive dysfunction in schizophrenia, part, via increasing cortical release. 5-HT(1A) agonism has been also suggested to contribute the ability increase The present study tested hypothesis that clozapine, olanzapine, risperidone, perhaps other atypical APDs, release rat medial prefrontal cortex (mPFC) receptor activation, a result blockade 5-HT(2A) receptors. M100907 (0.1 mg/kg), antagonist, significantly increased both S:(-)-sulpiride (10 antagonist devoid affinity, R:(+)-8-OH-DPAT (0.05 agonist, mPFC These effects were abolished by WAY100635 itself no effect on (0.2 mg/kg) reversed clozapine (20 olanzapine (1 risperidone Clozapine is direct acting partial whereas not. results suggest APDs blockade, regardless intrinsic promote stimulation DA release, provide additional evidence coadministration antagonists typical facilitate agonist activity.