Stimulation of α1-adrenoceptors in the rat medial prefrontal cortex increases the local in vivo 5-hydroxytryptamine release: reversal by antipsychotic drugs

Authors


Address correspondence and reprint requests to Dr Francesc Artigas, Department of Neurochemistry, Institut d' Investigacions Biomèdiques de Barcelona (CSIC), IDIBAPS, Rosselló, 161, 6th floor, 08036 Barcelona, Spain. E-mail: fapnqi@iibb.csic.es

Abstract

Pyramidal neurons of the medial prefrontal cortex (mPFC) project to midbrain serotonergic neurons and control their activity. The stimulation of prefrontal 5-HT2A and AMPA receptors increases pyramidal and serotonergic cell firing, and 5-hydroxytryptamine (5-HT) release in mPFC. As the mPFC contains abundant α1-adrenoceptors whose activation increases the excitability of pyramidal neurons, we examined the effects of their stimulation on local 5-HT release, using microdialysis. The application of the α1-adrenoceptor agonist cirazoline by reverse dialysis increased the prefrontal 5-HT release in a concentration-dependent manner, an effect antagonized by coperfusion of TTX, prazosin (α1-adrenoceptor antagonist), BAY × 3702 (5-HT1A agonist), NBQX (AMPA/KA antagonist) and 1S,3S-ACPD (mGluR II/III agonist), but not by MK-801 (NMDA antagonist). Cirazoline also enhanced the increase in 5-HT release induced by DOI (5-HT2A/2C agonist) and AMPA. In addition, M100907 (5-HT2A antagonist) but not SB-242084 (5-HT2C antagonist) reversed the cirazoline- and AMPA-induced 5-HT release. These results suggest that the stimulation of prefrontal α1-adrenoceptors activates pyramidal afferents to ascending serotonergic neurons. The effect of cirazoline was also reversed by coperfusion of classical (chlorpromazine, haloperidol) and atypical (clozapine, olanzapine) antipsychotics, which suggests that a functional antagonism of the α1-adrenoceptor-mediated activation of prefrontal neurons may partly underlie their therapeutic action.

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