Haloperidol increases the disruptive effect of alcohol on spatial working memory in rats: a dopaminergic modulation in the medial prefrontal cortex

Rationale. The prefrontal cortex (PFC) has been considered the anatomic site for working memory. The medial portion of the PFC (mPFC) is also part of a 'brain reward circuit' as constituted by the mesocorticolimbic dopaminergic system. Objective. This study examined the effects of acute administration of alcohol (ETOH) in the mPFC or systemically on the performance of 5-s or 1-h delayed tasks in an eight-arm radial maze. Effects of haloperidol (HAL), a dopamine antagonist, combined with ETOH, were also examined in a 1-h delayed task. Methods. Male Wistar rats trained in the radial maze and with bilateral cannulae implanted in the mPFC received intraperitoneal (IP) or intracortical (IC) drug administration. Results. As compared to saline (SAL) IC, ETOH IC in doses of 100 mug and 180 mug (5 min before session) increased significantly the number of errors in the 1-h and 5-s post-delay performance, respectively. HAL in doses with little or no effect alone IC (10 or 32 mug, 10 min before session) or IP (3.2 mg/kg, 35 min before session) increased the disruptive effect of ETOH IC (100 mug) on 1-h delayed task. Conclusions. These results showed that ETOH administered directly in the mPFC disrupts short- and long-term spatial working memory. The increase of the disruptive effect of ETOH produced by a dopaminergic blockage, particularly in the mPFC, suggests that the dopaminergic neurotransmission in this cortical area might modulate ETOH effects on spatial working memory.