4.7 Article

Nucleus incertus Orexin2 receptors mediate alcohol seeking in rats

期刊

NEUROPHARMACOLOGY
卷 110, 期 -, 页码 82-91

出版社

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2016.07.006

关键词

Alcohol; Nucleus incertus; Orexin; Reinstatement; Relaxin-3; Stress

资金

  1. National Health and Medical Research Council of Australia [1021227, 1079893, 1126330, 1020737]
  2. Polish Ministry of Science and Higher Education [N303 569939]
  3. National Science Centre [DEC-2012/05/D/NZ4/02984]
  4. EU (FP7-PEOPLE-IRSES) [PIRSES-GA-2012-318997]
  5. Besen Family
  6. Pratt Foundations
  7. Victorian State Government Infrastructure Program
  8. Melbourne International Research Scholarship
  9. Australian Postgraduate Award
  10. National Health and Medical Research Council of Australia [1079893] Funding Source: NHMRC

向作者/读者索取更多资源

Alcoholism is a chronic relapsing disorder and a major global health problem. Stress is a key precipitant of relapse in human alcoholics and in animal models of alcohol seeking. The brainstem nucleus incertus (NI) contains a population of relaxin-3 neurons that are highly responsive to psychological stressors; and the ascending NI relaxin-3/RXFP3 signalling system is implicated in stress-induced reinstatement of alcohol seeking. The NI receives orexinergic innervation and expresses orexin(1) (OX1) and orexin(2) (OX2) receptor mRNA. In alcohol-preferring (iP) rats, we examined the impact of yohimbine-induced reinstatement of alcohol seeking on orexin neuronal activation, and the effect of bilateral injections into NI of the OX1 receptor antagonist, SB-334867 (n = 16) or the OX2 receptor antagonist, TCS-OX2-29 (n = 8) on stress-induced reinstatement of alcohol seeking. We also assessed the effects of orexin-A on NI neuronal activity and the involvement of OX1 and OX2 receptors using whole cell patch-clamp recordings in rat brain slices. Yohimbine-induced reinstatement of alcohol seeking activated orexin neurons. Bilateral NI injections of TCS-OX2-29 attenuated yohimbine-induced reinstatement of alcohol seeking. In contrast, intra-NI injection of SB-334867 had no significant effect. In line with these data, orexin-A (600 nM) depolarized a majority of NI neurons recorded in corona] brain slices (18/28 cells), effects prevented by bath application of TCS-OX2-29 (10 mu M), but not SB-334867 (10 mu M). These data suggest an excitatory orexinergic input to NI contributes to yohimbine-induced reinstatement of alcohol seeking, predominantly via OX2 receptor signalling. Crown Copyright (C) 2016 Published by Elsevier Ltd. All rights reserved.

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