Enhanced Transient Striatal Dopamine Release and Reuptake in Knockout Rats.

Latrophilin-3 (LPHN3) is an adhesion G protein coupled receptor involved in regulating neuroplasticity. Variants of are associated with increased risk of attention-deficit hyperactivity disorder. Data from mouse, zebrafish, , and rat show that disruption of LPHN3 results in hyperactivity, and in the Sprague-Dawley knockout rat, exhibit deficits in learning and memory and changes in dopamine (DA) markers in the neostriatum. To determine the effects of deletion on DA neurotransmission, we compared the concentration, duration, and frequency of DA transients in KO and wild-type rats using fast-scan cyclic voltammetry in brain slices. KO rats showed higher release of DA, and the duration and interevent time were markedly decreased compared with wild-type rats. The data demonstrate that LPHN3 plays a heretofore unrecognized role in DA signaling and may represent a new target for small molecule regulation of DA neurotransmission with translational implications.