Serotonin transporter inhibition and 5-HT_2C receptor activation drive loss of cocaine-induced locomotor activation in DAT Val559 mice.

ABSTRACT: Dopamine (DA) signaling dysfunction is believed to contribute to multiple neuropsychiatric disorders including attention-deficit/hyperactivity disorder (ADHD). The rare DA transporter (DAT) coding substitution Ala559Val found in subjects with ADHD, bipolar disorder and autism, promotes anomalous DA efflux in vitro and, in DAT Val559 mice, leads to increased reactivity to imminent handling, waiting impulsivity, and enhanced motivation for reward. Here, we report that, in contrast to amphetamine and methylphenidate, which induce significant locomotor activation, cocaine administration to these mice elicits no locomotor effects, despite retention of conditioned place preference (CPP). Additionally, cocaine fails to elevate extracellular DA. Given that amphetamine and methylphenidate, unlike c

SUBMITTER: Stewart A 

PROVIDER: S-EPMC6462012 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature