When systemically administered within an interval of 2h, previous administration of methylphenidate (10mg/kg, intraperitoneal (i.p.)) did not modify locomotor activation induced by methamphetamine. On the other hand, previous administration of methamphetamine (1mg/kg,i.p.) markedly potentiated methylphenidate-induced motor activation. With in vivo microdialysis experiments, Selleck Lonafarnib methamphetamine and methylphenidate were found to increase DA extracellular levels in the nucleus accumbens (NAs). Methamphetamine, but not methylphenidate, significantly increased the extracellular levels of serotonin (5-HT) in the NAs. Methamphetamine-induced 5-HT release remained significantly elevated for more than 2h after its

administration, suggesting that the increased 5-HT could be responsible for the potentiation of methylphenidate-induced locomotor activation. In fact, previous administration

of the 5-HT uptake blocker fluoxetine (10mg/kg,i.p.) also potentiated the motor activation induced by methylphenidate. A selective 5-HT(1B) receptor antagonist (GR 55562; 1mg/kg), but not a 5-HT(2) receptor antagonist (ritanserin;2mg/kg,i.p.), counteracted the effects of methamphetamine and fluoxetine on the motor activation induced by methylphenidate. Furthermore, a 5-HT(1B) receptor agonist (CP94253;1-10mg/kg,i.p.) strongly and dose-dependently potentiated methylphenidate-induced locomotor activation. The 5-HT(1B) receptor-mediated modulation of methylphenidate-induced locomotor activation in rat could have implications for the treatment of ADHD.”
“Neural mechanisms underlying the reinforcing effects Volasertib supplier of nicotine and other

drugs have been widely studied and are known to involve the ventral striatum, which is part of the mesocorticolimbic dopamine system. In contrast, mechanisms of nicotine withdrawal have received less attention although subjective withdrawal likely contributes to the difficulty of quitting. The goal of this study was to determine PJ34 HCl if nicotine withdrawal was associated with alterations of cerebral blood flow (CBF) in ventral striatum. Twelve smokers, moderately dependent on nicotine, underwent MR dynamic susceptibility contrast (DSC) imaging at baseline, after overnight withdrawal from nicotine, and after nicotine replacement. DSC images were used to calculate CBF in three regions of interest: ventral striatum, thalamus, and medial frontal cortex. Subjective withdrawal symptoms were measured at each time point. In spite of significant subjective withdrawal symptoms, there was no main effect of withdrawal on CBF in the three regions. However, there was a significant correlation between the increase in withdrawal symptoms and a reduction in thalamic CBF. In contrast to withdrawal, nicotine replacement significantly increased CBF in ventral striatum. Our findings are consistent with the known role of ventral striatum in drug reward.