Suboptimal foraging decisions and involvement of the ventral tegmental area in human opioid addiction

Addiction is marked by a tendency to exploit sources of reward despite diminishing returns. This behavior is aptly captured by animal patch-foraging models that have recently been extended to humans. Dopamine and norepinephrine centrally mediate addictive behavior and activity in both catecholaminergic systems is proposed to reflect the computations necessary for optimal foraging. However, the specific neural bases of excessive foraging and their role in human addiction are largely unknown. To address this gap, we studied the behavior of people with and without opioid use disorder (OUD) on a patch-foraging task in which they made serial decisions to "harvest" a depleting resource ("patch") for reward or incur a varying cost to "travel" to a replenished patch. In a subset of participants, we used high-resolution neuromelanin-sensitive MRI to image neuromelanin concentration, a proxy for long-term catecholaminergic function, in distinct dopaminergic nuclei (ventral tegmental area, substantia nigra subregions) and the noradrenergic locus coeruleus. While all participants were sensitive to the long-run reward rates of different patch-foraging environments, OUD participants stayed in reward patches longer than optimal - markedly overharvesting a source of reward despite its declining value - and this correlated with more chronic drug use. Overharvesting was selectively associated with lower neuromelanin signal in the ventral tegmental area but not other dopaminergic nuclei, nor the locus coeruleus. Our findings suggest that foraging decisions relevant to addiction involve a ventral-tegmental-area circuit that may signal reward rates in dynamic environments and implicate this circuit in maladaptive reward pursuit in human addiction to opioids. ### Competing Interest Statement The authors have declared no competing interest.