1. ¹Department of Experimental Biology 'B. Loddo,' University of Cagliari, Cagliari, Italy
2. ²Center of Excellence for Neurobiology of Dependence, University of Cagliari, Cagliari, Italy
3. ³Unit of Neuropsychopharmacology, CNR Institute for Neuroscience, University of Cagliari, Cagliari, Italy

Correspondence: Professor L Dazzi, Department of Experimental Biology 'B. Loddo,' Neuroscience Section, Cittadella Universitaria, Monserrato, SS. 554, Km 4.500, 09042 Cagliari, Italy. Tel: +39 070 675 4169; Fax: +39 070 675 4166; E-mail: dazzi@unica.it

Received 1 February 2006; Revised 5 April 2006; Accepted 22 May 2006; Published online 12 July 2006.

Abstract

The influence of the estrous cycle on dopamine levels in the rat medial prefrontal cortex under basal and ethanol-stimulated conditions was evaluated by microdialysis. The basal dopamine concentration in the dialysate varied markedly during the estrous cycle, being highest in estrus and lowest in proestrus. Furthermore, a challenge intraperitoneal administration of ethanol (0.5 g/kg) induced a significant increase in dopaminergic output (+50%) during estrus but had no effect in diestrus or proestrus. Ovariectomy or pretreatment with either finasteride (a 5-reductase inhibitor) or clomiphene (an estrogen receptor antagonist) prevented this ethanol-induced increase in dopamine concentration. The effect of ethanol was restored in ovariectomized rats by pretreatment with estrogen but not by that with progesterone. Our results thus show that the basal levels of dopamine in the prefrontal cortex are dependent on the phase of the estrous cycle. Furthermore, this dependence appears to be attributable to the effects of ovarian steroid hormones and results in a differential sensitivity of the dopaminergic neurons to ethanol. The hormone-induced changes in the activity of these neurons might contribute to the differences in drug sensitivity and mood state apparent among phases of the estrous cycle and between the sexes.