Psychopharmacology 2007-04-01

Medial prefrontal cortical alpha1 adrenoreceptor modulation of the nucleus accumbens dopamine response to stress in Long-Evans rats.

Brid Nicniocaill, Alain Gratton

Index: Psychopharmacology 191(3) , 835-42, (2007)

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Abstract

The medial prefrontal cortex (PFC) receives stress-sensitive dopamine (DA) and noradrenergic (NE) projections from the ventral tegmental area and locus coeruleus, respectively, and evidence from various sources point to a complex functional interaction between these two systems. Stress will also stimulate DA transmission in the nucleus accumbens (NAcc), and our previous work has shown that this response is under the indirect inhibitory control of a DA-sensitive mechanism in PFC.We examined the possibility that the NAcc DA stress response is also modulated by prefrontal cortical NE.We used voltammetry to study in freely behaving rats the effects of local applications of alpha(1) (benoxathian 0.1, 1, 10 nmol), alpha(2) (SKF86466), and beta(1/2) (alprenolol) receptor selective antagonists into the PFC on the NAcc DA response to tail-pinch stress.The NAcc DA stress response was dose-dependently inhibited by local PFC blockade of alpha(1) receptors. Additional tests revealed, however, that the DA stress response in NAcc is unaffected after local alpha(1) receptor activation with cirazoline. Furthermore, at equivalent doses, neither alpha(2) nor beta(1/2) receptor blockade significantly affected the NAcc DA stress response.These data indicate that stress-induced activation of subcortical DA transmission is modulated by the NE input to PFC acting at alpha(1) receptors. They suggest that, under normal circumstances, this system exerts a facilitatory or enabling influence on the NAcc DA stress response.