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

Morgan H. James, Janine L. Charnley, Emily M. Levi, Emma Jones, Jiann Wei Yeoh, Doug W. Smith, Christopher V. Dayas

Research output: Contribution to journalArticlepeer-review

97 Scopus citations

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 g; 0, 1 or 3 g, respectively) prior to reinstatement testing elicited by presenting cocaine-paired stimuli (S +). The effect of VTA-directed injections of SB-334867 (0 or 3 g) on locomotor activity was also assessed. Intra-VTA, but not -PVT, SB-334867 dose-dependently attenuated S +-induced reinstatement (3 g 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.

Original languageEnglish (US)
Pages (from-to)684-690
Number of pages7
JournalInternational Journal of Neuropsychopharmacology
Volume14
Issue number5
DOIs
StatePublished - Jun 2011
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

Keywords

  • Cocaine
  • orexin
  • paraventricular thalamus
  • relapse
  • ventral tegmental area

Fingerprint Dive into the research topics of 'Orexin-1 receptor signalling within the ventral tegmental area, but not the paraventricular thalamus, is critical to regulating cue-induced reinstatement of cocaine-seeking'. Together they form a unique fingerprint.

Cite this