Hypocretins (hcrt), also known as orexins, play a critical role in reward-seeking behavior for natural rewards and drugs of abuse. The mesolimbic dopamine pathway that projects from the ventral tegmental area (VTA) to the nucleus accumbens (NAc) is critically involved in the neural mechanisms underlying reward-seeking and motivation. Hcrt immunopositive fibers densely project to the shell of the nucleus accumbens (NAcSh), suggesting that the NAcSh might be a site for the interaction between hcrt and dopaminergic modulation of reward-seeking behavior. While it is known that hcrt action in the VTA can increase dopamine in the NAc, it has not been determined if hcrt released locally at dopaminergic terminals in the NAcSh can modulate dopamine concentration. Here, we use fast scan cyclic voltammetry (FSCV) in forebrain slices containing the NAcSh to determine whether hcrt can alter evoked dopamine concentration. We found bath application of hcrt-1 increases phasically evoked dopamine release, without altering reuptake at dopamine terminals in the NAcSh. Hcrt-1-induced potentiation of dopamine concentration was inhibited by SB334867, a hcrt receptor 1 antagonist, as well as ionotropic glutamate receptor antagonists, AP-5, CNQX and DNQX. Taken together, these results suggest that local hcrt-1 can modulate dopamine in the NAcSh and may play a role in reward-seeking and appetitive behaviors.
Keywords: hypocretin, orexin, dopamine, nucleus accumbens shell, voltammetry, glutamate
Citation: Patyal R, Woo EY and Borgland SL (2012) Local hypocretin-1 modulates terminal dopamine concentration in the nucleus accumbens shell. Front. Behav. Neurosci. 6:82. doi:10.3389/fnbeh.2012.00082
Received: 15 September 2012; Accepted: 05 November 2012;
Published online: 28 November 2012.
Edited by:Benjamin Boutrel, Lausanne University Hospital, Switzerland
Reviewed by:Mitchell Roitman, University of Illinois at Chicago, USA
Copyright © 2012 Patyal, Woo and Borgland. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.
*Correspondence: Stephanie L. Borgland, Department of Anesthesiology, Pharmacology and Therapeutics, The University of British Columbia, 212-2176 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada. e-mail: firstname.lastname@example.org
†These authors equally contributed to this work.