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The hypothalamus and the neurobiology of drug seeking

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Abstract

The hypothalamus is a neural structure critical for expression of motivated behaviours that ensure survival of the individual and the species. It is a heterogeneous structure, generally recognised to have four distinct regions in the rostrocaudal axis (preoptic, supraoptic, tuberal and mammillary). The tuberal hypothalamus in particular has been implicated in the neural control of appetitive motivation, including feeding and drug seeking. Here we review the role of the tuberal hypothalamus in appetitive motivation. First, we review evidence that different regions of the hypothalamus exert opposing control over feeding. We then review evidence that a similar bi-directional regulation characterises hypothalamic contributions to drug seeking and reward seeking. Lateral regions of the dorsal tuberal hypothalamus are important for promoting reinstatement of drug seeking, whereas medial regions of the dorsal tuberal hypothalamus are important for inhibiting this drug seeking after extinction training. Finally, we review evidence that these different roles for medial versus lateral dorsal tuberal hypothalamus in promoting or preventing reinstatement of drug seeking are mediated, at least in part, by different populations of hypothalamic neurons as well as the neural circuits in which they are located.

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Acknowledgments

The preparation of this manuscript was supported by grants from the National Health and Medical Research Council (510199; 630406). GPM is an Australian Research Council QEII Fellow (DP0877430).

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Correspondence to Nathan J. Marchant or Gavan P. McNally.

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Marchant, N.J., Millan, E.Z. & McNally, G.P. The hypothalamus and the neurobiology of drug seeking. Cell. Mol. Life Sci. 69, 581–597 (2012). https://doi.org/10.1007/s00018-011-0817-0

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