Time-of-Day Differences in Dopamine Clearance in the Rat Medial Prefrontal Cortex and Nucleus Accumbens

Circadian rhythms influence cocaine-seeking behavior in rats, and this behavior may be mediated by variability in the rate of extracellular dopamine clearance across the day:night cycle. We used rotating disk electrode voltammetry to examine dopamine clearance and inhibition of clearance by cocaine in the rat medial prefrontal cortex (mPFC) and nucleus accumbens (NAc). Rats were housed under light:dark conditions (LD, 12 h:12 h) or in constant darkness (DD), the latter given just prior to the day of sacrifice. Tissue was collected at 4-h intervals under LD and DD conditions. Under LD, dopamine clearance in both brain regions was greatest at 4 h after lights on. Under DD, there was a blunted but still rhythmic pattern of dopamine clearance across the 24-h cycle. Cocaine-induced inhibition of dopamine clearance in the mPFC was not different across the day:night cycle in rats under LD. Paradoxically, under DD, dopamine clearance in the mPFC was enhanced by cocaine at ZT16, 4 h into the subjective night, and only minimally inhibited at other times. In the NAc, cocaine inhibition of dopamine clearance was lowest at ZT4 under LD, and did not vary under DD. We conclude that dopamine clearance varies both in a diurnal and possibly in a circadian manner in the mPFC, and in a diurnal manner in the NAc. These results indicate that light itself may be used to manipulate molecules implicated in drug addiction. Synapse 62:877-885, 2008. (C) 2008 Wiley-Liss, Inc.