Grant: Master's Award: Canada Graduate Scholarships

Circadian rhythms are daily fluctuations in physiology and behavior. Disruptions in these rhythms are associated with various disorders, including drug addiction. There is evidence for a reciprocal relation between circadian rhythm disruptions and drug addiction, but the mechanisms underlying this relation remain to be investigated. One molecule likely involved in the relation between circadian rhythm disruptions and drug addiction is the clock protein Period2 (PER2). Previous work from my laboratory has shown that PER2 is rhythmically expressed in the ventral striatum (VS), a brain region known to play a key role in motivation, reward, and behavioral responses to addictive drugs. In addition, several studies have shown that global genetic suppression of PER2 expression alters behavioral responses to addictive drugs. These studies suggest that PER2 expression is part of the mechanisms whereby addictive drugs influence behavior, but no specific brain region where PER2 expression is part of these mechanisms has been identified so far. To determine whether PER2 expression in the VS is part of the mechanisms whereby addictive drugs influence behavior, I will suppress PER2 expression in the VS using RNA interference in rats. I will assess whether this suppression prevents amphetamine-induced sensitization of locomotor activity, a finding that would suggest that PER2 expression plays a role in mediating the sensitizing effects of repeated amphetamine administration on behavior. Such a finding could have implications for the understanding of the mechanisms potentially underlying the relation between circadian rhythm disruptions and drug addiction.