Science Links Japan | Mechanism of action of atypical antipsychotic drugs. A possible involvement of the interaction of glutamate and serotonergic systems in the medial prefrontal cortex.

Mechanism of action of atypical antipsychotic drugs. A possible involvement of the interaction of glutamate and serotonergic systems in the medial prefrontal cortex.

Accession number;02A0472890

Title;Mechanism of action of atypical antipsychotic drugs. A possible involvement of the interaction of glutamate and serotonergic systems in the medial prefrontal cortex.

Author; KAJIHATA TOSHIO (Kyudai Daigakuin'igakukenkyuin Seishinbyotaiigaku) KUROKI TOSHIHIDE (Kyudai Daigakuin'igakukenkyuin Seishinbyotaiigaku) MOTOMURA KEISUKE (Kyudai Daigakuin'igakukenkyuin Seishinbyotaiigaku) KANCHIKU IZUMI (Kyushu Univ., School of Sciences, JPN) HONDO HISAO (Kokuritsuhizenryoyosho Rinshokenkyubu) NAKAHARA TATSUO (Kyushu Univ., School of Sciences, JPN) TASHIRO NOBUTADA (Kyudai Daigakuin'igakukenkyuin Seishinbyotaiigaku)

Journal Title;Annual Report of the Pharmacopsychiatry Research Foundation

Journal Code:Y0939A

ISSN:0286-7591

VOL.;NO.34;PAGE.168-175(2002)

Figure&Table&Reference;FIG.3, REF.27

Pub. Country;Japan

Language;Japanese

Abstract;Atypical antispychotic drugs such as clozapine have been hypothesized to improve cognitive symptoms of schizophrenia by the modulation of prefrontal activity of glutamate(Glu) neurons via serotonin(5-HT)2A receptors. In this study, we examined the effects of different types of antispychotic drugs on high K+-evoked extracellular Glu levels in the medial prefrontal cortex(mPFC), using in vivo microdialysis of awake freely moving rats. Since high K+-evoked extracellular Glu levels in rat mPFC was TTX- and Ca2+-sensitive, it may reflect glutamatergic neuronal activity. Clozapine, olanzapine and risperidone at at least one dose significantly attenuated the high K+-evoked increase in extracellular Glu levels in the mPFC, while haloperidol had no effect on prefrontal Glu levels. The musucarinic receptor antagonist scopolamine, but not the 5-HT2A/2C antagonist ritanserin, significantly attenuated high K+-evoked extracellular Glu levels in the mPFC. In is thus unlikely that 5-HT2A receptor antagonism solely accounts for the mechanism of action of atypical antipsychotic drugs on glutamatergic transmission. The effect of clozapine and olanzapine may be attributed at least in part to the blockade of muscarinic receptors. These results lead to a testable hypothesis that the ability of atypical antipsychotic drugs to regulate the activity of glutamatergic projections to the mPFC may contribute to the superior effects of these drugs on cognitive symptoms of schizophrenia. (author abst.)

Related Articles;