a1 Neurobiology of Addiction Laboratory, School of Biomedical Sciences and Pharmacy and the Centre for Brain and Mental Health Research, University of Newcastle and the Hunter Medical Research Institute, Newcastle, NSW, Australia
Orexinergic signalling is critical to drug relapse-like behaviour; however, the CNS sites(s) of action remain unknown. Two candidate brain regions are the paraventricular thalamus (PVT) and ventral tegmental area (VTA). We assessed the effect of intra-PVT or -VTA administration of the orexin-1 receptor (OrxR1) antagonist SB-334867 on discriminative cue-induced cocaine-seeking. Animals received either PVT- or VTA-directed SB-334867 (0, 3 or 6 μg; 0, 1 or 3 μg, respectively) prior to reinstatement testing elicited by presenting cocaine-paired stimuli (S+). The effect of VTA-directed injections of SB-334867 (0 or 3 μg) on locomotor activity was also assessed. Intra-VTA, but not -PVT, SB-334867 dose-dependently attenuated S+-induced reinstatement (3 μg dose, p<0.01). Intra-VTA SB-334867 had no effect on locomotor activity. We conclude that OrxR1 signalling within the VTA, but not the PVT, mediates cue-induced cocaine-seeking behaviour. We hypothesize that blockade of VTA OrxR1 signalling may reduce nucleus accumbens dopamine in response to drug cue presentation.
(Received October 29 2010)
(Reviewed December 28 2010)
(Revised January 20 2011)
(Accepted February 16 2011)
(Online publication March 29 2011)
c1 Address for correspondence: Dr C. V. Dayas, School of Biomedical Sciences & Pharmacy, University of Newcastle and the Hunter Medical Research Institute, Newcastle, NSW 2308, Australia. Tel.: +61 2 4921 5618 Fax: +61 2 4921 8667 Email: Christopher.Dayas@newcastle.edu.au