Gene-dose dependent effects of methamphetamine on interval timing in dopamine-transporter knockout mice

摘要: The dopamine transporter (DAT) is the major regulator of spatial and temporal resolution dopaminergic neurotransmission in brain. Hyperdopaminergic mice with DAT gene deletions were evaluated for their ability to perform duration discriminations seconds-to-minutes range. -/- unable demonstrate control behavior either fixed-interval or peak-interval timing procedures, whereas +/- similar +/+ under normal conditions. Low moderate-dose methamphetamine (MAP) challenges indicated that less sensitive clock-speed enhancing effects MAP compared mice. In contrast, more vulnerable than disruptive at high doses as revealed by elevation response rate right hand tail Gaussian-shaped functions. Moreover, this treatment made functionally equivalent terms loss control. Taken together, these results importance interval cortico-striatal circuits potential link dysfunctions schizophrenia drug abuse.