The hypothalamus and the neurobiology of drug seeking

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.

The reinstatement model of drug relapse: recent neurobiological findings, emerging research topics, and translational research

“…McNally and colleagues continued their investigation of the role of sub-regions of hypothalamus and thalamus and their projections in context-induced reinstatement of alcoholic beer seeking in the drug (A) context, as well as extinction of alcohol seeking in the non-drug (B) context (Marchant et al 2012; Millan et al 2011). …”

Motivational activation: a unifying hypothesis of orexin/hypocretin function

“…Numerous reports have since shown that seeking for all major addictive drugs involves orexin neurons 36 . Reminiscent of their role in food seeking, orexins are preferentially involved in highly motivated drug seeking (for example, under progressive ratio reinforcement schedules or seeking that is triggered by salient external stimuli such as drug-paired cues or stressors) 30,36,39,41–43 . Acute drug withdrawal also involves orexins, leading some to speculate that orexin neuron activity during withdrawal facilitates drug seeking to alleviate this specific ‘drug need state’ 42 .…”

Histone-Mediated Epigenetics in Addiction

“…The first time drugs of abuse are used (e.g., psychostimulants, alcohol, opioids, nicotine, Δ 9 tetrahydro-cannabinol), brain regions in both reward (i.e., ventral tegmental area, striatum, nucleus accumbens core, thalamus) and learning (basolateral and central nucleus of the amygdala, medial prefrontal cortex, hippocampus) centers share excitatory information (reviewed in Koob & Volkow 2010; Marchant et al, 2012). Some of these structures serve a primary role in particular stages of addiction (e.g., binge/intoxication, withdrawal/negative affect, and preoccupation/anticipation/craving; Koob & Volkow, 2010) and memory processes (i.e., encoding, consolidation, and retrieval; e.g., Bernardi et al, 2009; Lalumiere et al, 2012), yet many of these regions can be recruited throughout each process.…”