Stimulation of α1-adrenoceptors in the rat medial prefrontal cortex increases the local in vivo 5-hydroxytryptamine release: reversal by antipsychotic drugs
Article first published online: 4 FEB 2004
Journal of Neurochemistry
Volume 87, Issue 4, pages 831–842, November 2003
How to Cite
Amargós-Bosch, M., Adell, A., Bortolozzi, A. and Artigas, F. (2003), Stimulation of α1-adrenoceptors in the rat medial prefrontal cortex increases the local in vivo 5-hydroxytryptamine release: reversal by antipsychotic drugs. Journal of Neurochemistry, 87: 831–842. doi: 10.1046/j.1471-4159.2003.02044.x
- Issue published online: 4 FEB 2004
- Article first published online: 4 FEB 2004
- Received March 6, 2003; revised manuscript received June 17, 2003; accepted July 14, 2003.
- glutamate receptors;
- 5-HT release;
- 5-HT2A receptors;
- medial prefrontal cortex;
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.