Role of the Dopamine Transporter in the Differential Cocaine-Induced Locomotor Activation of Inbred Long-Sleep and Short-Sleep Mice

Abstract

The locomotor-stimulant effects of cocaine, mediated through inhibition of the dopamine transporter (DAT), can be influenced by environmental factors. Previously, we found that following a short exposure to the testing environment, cocaine induces greater locomotor activation in inbred long-sleep (ILS) mice, compared to inbred short-sleep (ISS) mice. In the present study, all animals received prolonged habituation to the testing chambers prior to cocaine injection, and the results were compared with those from our previous study. When mice were tested with saline on day 1 and with either saline or cocaine (10-20 mg/kg) on day 2, we observed significant locomotor stimulation in ILS, but not ISS, mice at all tested doses of cocaine. Thus, prolonged habituation does not alter the differential responsiveness of these two strains of mice to cocaine. We found no strain differences in striatal cocaine levels. However, [3 H]WIN 35,428 binding studies showed a lower number of striatal DATs in ILS, compared to ISS, mice. In vivo analysis of striatal DAT activity revealed not only that ILS mice cleared exogenously applied DA more slowly than ISS mice, but also that cocaine (10 mg/kg) decreased DA clearance selectively in ILS mice. Thus, functional differences in striatal DATs between ILS and ISS mice likely contribute to the differential behavioral activation of cocaine in these two mouse strains.

CB1‐independent inhibition of dopamine transporter activity by cannabinoids in mouse dorsal striatum

“…Chronoamperometric recordings of AM251 (Fig. 5) were reminiscent of those observed after injection of classic DAT inhibitors such as cocaine (Sabeti et al 2003a;Hanania et al 2004) and showed a gradual increase of DA signal amplitude and T 80 peaking between 25-35 min after drug administration.…”

Mice expressing markedly reduced striatal dopamine transporters exhibit increased locomotor activity, dopamine uptake turnover rate, and cocaine responsiveness

“…Indirect saturation binding assays were performed using a previously described protocol (Hanania et al, ). Briefly, striata were dissected out from the DAT‐LE mice and their WT littermates, homogenized in ice‐cold assay buffer (30 mM NaH 2 PO 4 , 15 mM Na 2 HPO 4 , and 0.32 M sucrose; pH 7.4) using a sonicator, and centrifuged at 20,000 g for 20 min at 4°C.…”

Electroacupuncture reduces scopolamine-induced amnesia via mediating the miR-210/SIN3A and miR-183/SIN3A signaling pathway

“…Specially, T Novel refers to time spent with novel object and T Familiar refers to time spent with familiar object. And rearing, NCD and locomotive activity were also evaluated (Matsumoto 2014;Hanania 2004) and involved in the statistical analysis as potential confounding factors.…”