The neurobiology of abstinence-induced reward-seeking in males and females

Drugs of abuse and highly palatable foods (e.g. high fat or sweet foods) have powerful reinforcing effects, which can lead to compulsive and addictive drives to ingest these substances to the point of psychopathology and self-harm–specifically the development of Substance Use Disorder (SUD) and obesity. Both SUD and binge-like overeating can be defined as disorders in which the salience of the reward (food or drug) becomes exaggerated relative to, and at the expense of, other rewards that promote well-being. A major roadblock in the treatment of these disorders is high rates of relapse after periods of abstinence. It is common, although not universal, for cue-induced craving to increase over time with abstinence, often triggered by cues previously paired with the reinforcing substance. Accumulating evidence suggests that similar neural circuits and cellular mechanisms contribute to abstinence-induced and cue-triggered seeking of drugs and palatable food. Although much research has focused on the important role of corticolimbic circuitry in drug-seeking, our goal is to expand focus to the more recently explored hypothalamic–thalamic–striatal circuitry. Specifically, we review how connections, and neurotransmitters therein, among the lateral hypothalamus, paraventricular nucleus of the thalamus, and the nucleus accumbens contribute to abstinence-induced opioid- and (high fat or sweet) food-seeking. Given that biological sex and gonadal hormones have been implicated in addictive behavior across species, another layer to this review is to compare behaviors and neural circuit-based mechanisms of abstinence-induced opioid- or food-seeking between males and females when such data is available.