Nicotine self-administration in the rat: effects of hypocretin antagonists and changes in hypocretin mRNA
- 24 February 2010
- journal article
- research article
- Published by Springer Science and Business Media LLC in Psychopharmacology
- Vol. 209 (2), 203-212
- https://doi.org/10.1007/s00213-010-1792-0
Abstract
The hypocretin (hcrt) system has been implicated in addiction-relevant effects of several drugs, but its role in nicotine dependence has been little studied. These experiments examined the role of the hcrt system in nicotine reinforcement. Rats were trained for nicotine self-administration (NSA) on fixed-ratio schedules. The effects of acute, presession treatments with the hcrtR1 antagonist SB334867 and the hcrtR1/2 antagonist almorexant were examined on NSA maintained on a fixed-ratio (FR) 5 schedule. Gene expression for the hcrt system (mRNA for hcrt, hcrtR1, and hcrtR2) was measured in animals following NSA on a FR 1 schedule for a 19-day period. The hcrtR1 antagonist SB334867 and the hcrtR1/2 antagonist almorexant both reduced NSA dose-dependently (significantly at doses of 30 and 300 mg/kg, respectively); SB334867 did not affect food-maintained responding whereas almorexant (at the 300 mg/kg) did. Tissue from animals collected 5 h after self-administration showed an increase in hcrtR1 mRNA in the arcuate nucleus compared to control subjects. In tissue collected immediately after a similar 19-day self-administration period, mRNA for hcrtR1 was decreased in the rostral lateral hypothalamus compared to controls. These data confirm a previous report (Hollander et al., Proc Natl Acad Sci U S A 105:19480–19485, 2008) that the hypocretin receptor hcrtR1 is activated in nicotine reinforcement and in addition show that both the arcuate nucleus and lateral hypothalamus are sites at which hcrt receptor mechanisms may influence reinforcement. Different patterns of mRNA expression at different times after NSA suggest that changes in the hcrt system may be labile with time.This publication has 63 references indexed in Scilit:
- The hypocretin–orexin system regulates cocaine self‐administration via actions on the mesolimbic dopamine systemEuropean Journal of Neuroscience, 2010
- Role of lateral hypothalamic orexin neurons in reward processing and addictionNeuropharmacology, 2009
- Orexin/hypocretin signaling at the orexin 1 receptor regulates cue‐elicited cocaine‐seekingEuropean Journal of Neuroscience, 2009
- Biochemical and behavioural characterization of EMPA, a novel high‐affinity, selective antagonist for the OX2 receptorBritish Journal of Pharmacology, 2009
- Activation of orexin/hypocretin projections to basal forebrain and paraventricular thalamus by acute nicotineBrain Research Bulletin, 2008
- Insular hypocretin transmission regulates nicotine rewardProceedings of the National Academy of Sciences of the United States of America, 2008
- A Role for Brain Stress Systems in AddictionNeuron, 2008
- Inhibition of orexin-1/hypocretin-1 receptors inhibits yohimbine-induced reinstatement of ethanol and sucrose seeking in Long–Evans ratsPsychopharmacology, 2008
- Differential effects of the hypocretin 1 receptor antagonist SB 334867 on high‐fat food self‐administration and reinstatement of food seeking in ratsBritish Journal of Pharmacology, 2008
- The orexin system regulates alcohol‐seeking in ratsBritish Journal of Pharmacology, 2006