Accumbal α-adrenoceptors, but not β-adrenoceptors, regulate behaviour that is mediated by reserpine-sensitive storage vesicles

Abstract

It has previously been demonstrated that mesolimbic α-adrenoceptors, but not β-adrenoceptors, control the release of dopamine that is derived from reserpine-sensitive storage vesicles. The aim of the present study was to investigate whether these storage vesicles also regulate α-adrenoceptor-mediated or β-adrenoceptor-mediated changes in behaviour. Accordingly, rats were pretreated with reserpine before the α-adrenoceptor antagonist phentolamine or the β-adrenoceptor agonist isoproterenol was locally applied to the nucleus accumbens. Both phentolamine and isoproterenol increased the duration of walking, rearing and grooming and decreased the duration of sitting. Reserpine counteracted the behavioural response elicited by phentolamine but not by isoproterenol. The results of the present study demonstrate that mesolimbic α-adrenoceptors, but not β-adrenoceptors, regulate behaviour that is mediated by reserpine-sensitive storage pools. It is hypothesized that the observed α-adrenoceptor-mediated increase in locomotor activity is due to the α-adrenoceptor-mediated increase in the release of accumbal intravesicular dopamine. Our finding that α-adrenoceptors inhibit, whereas β-adrenoceptors stimulate, locomotor activity may help explain why noradrenaline or environmental stressors have previously been found to have opposing effects on the regulation of behaviour.

Noradrenaline-induced release of newly-synthesized accumbal dopamine: differential role of alpha- and beta-adrenoceptors

“…As expected, intra-accumbens infusion of PA and ISO increased accumbal DA levels in rats treated with the solvent of AMPT (Figures 4 , 6 ). This accumbal DA increase may very well explain the previously reported increase in locomotor activity observed following the inhibition and stimulation of accumbal alpha- and beta-adrenoceptors, respectively (Verheij et al, accepted ). It has been demonstrated previously that the DA increase following intra-accumbens administration of PA and ISO are dose-dependent and receptor-specific (Tuinstra and Cools, 2000 ).…”

“…Our study underlines the view that mesolimbic noradrenaline fulfills many functions that are, up to now, primarily ascribed to mesolimbic DA (Cools and Tuinstra, 2003 ). Indeed, both accumbal DA and accumbal noradrenaline were found not only to regulate locomotor activity (Pijnenburg et al, 1975 ; Costall et al, 1976 ; Cools et al, 1987 ; Ikeda et al, 2007 ; Verheij et al, accepted ), sensorimotor gating (Alsene et al, 2010 , 2011 ) and anxiety (Roozendaal and Cools, 1994 ; Kochenborger et al, 2012 ), but also more complex behaviors that are depending on learning and memory (Tuinstra et al, 2000 , 2002 ; Kerfoot et al, 2008 ; Kerfoot and Williams, 2011 ) processes (for review: Verheij and Cools, 2008 ).…”