Orexin-1 receptor signalling within the ventral tegmental area, but not the paraventricular thalamus, is critical to regulating cue-induced reinstatement of cocaine-seeking

Int J Neuropsychopharmacol. 2011 Jun;14(5):684-90. doi: 10.1017/S1461145711000423. Epub 2011 Mar 29.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzoxazoles / pharmacology*
  • Cocaine / pharmacology
  • Cocaine-Related Disorders / metabolism*
  • Cocaine-Related Disorders / physiopathology
  • Cues
  • Dopamine Uptake Inhibitors / pharmacology
  • Extinction, Psychological / drug effects
  • Male
  • Motor Activity / drug effects
  • Naphthyridines
  • Orexin Receptors
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, G-Protein-Coupled / antagonists & inhibitors
  • Receptors, G-Protein-Coupled / physiology*
  • Receptors, Neuropeptide / antagonists & inhibitors
  • Receptors, Neuropeptide / physiology*
  • Self Administration
  • Thalamus / drug effects*
  • Thalamus / metabolism
  • Urea / analogs & derivatives*
  • Urea / pharmacology
  • Ventral Tegmental Area / drug effects*
  • Ventral Tegmental Area / physiology

Substances

  • 1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea
  • Benzoxazoles
  • Dopamine Uptake Inhibitors
  • Naphthyridines
  • Orexin Receptors
  • Receptors, G-Protein-Coupled
  • Receptors, Neuropeptide
  • Urea
  • Cocaine