The role of the preoptic area in response to cocaine



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The preoptic area of the hypothalamus is ideally suited to modulate the behavioral and neural response to drugs of abuse such as cocaine. The preoptic area is broken up into two major subregions the medial preoptic area (mPOA) and the lateral preoptic area (LPO), both of which send dense projections to mesolimbic dopamine system. Specifically, both project to the ventral tegmental area (VTA), a brain region implicated in drug-associated reward. Previous work has demonstrated the mPOA is involved in the behavioral and neural response to cocaine in female rats, however the mechanism through which the mPOA modulates response to cocaine is unclear. Whether or not the mPOA also plays a role in response to cocaine in male rats is still not clear. Furthermore the role of the adjacent LPO in response to cocaine is unexplored, despite its anatomical relationship to the VTA and involvement in intracranial self-stimulation. Here I demonstrate that estradiol acts in the mPOA of female rats to modulate response to cocaine. Specifically, microinjections of estradiol directly into the mPOA one day prior to cocaine administration increase cocaine-induced dopamine levels in the nucleus accumbens. The mPOA is also involved in the behavioral regulation of response to cocaine in male rats, as mPOA lesions enhanced cocaine-induced locomotion and reward. Finally, activation of the LPO, with pharmacology or chemogenetics, potentiates reinstatement of cocaine seeking, an animal model of drug relapse. Together these results demonstrate that the preoptic area as a whole is involved in the regulation of the neural and behavioral response to cocaine and shed light on underlying regulatory mechanisms.