Previous work in both METH-pretreated animals and the 6-hydroxydopamine model of Parkinson’s disease suggests that a disruption of phasic DA signaling, which is important for learning and goal-directed behavior, may be such a link. However, previous studies

used electrical stimulation to elicit phasic-like DA responses and were also performed under anesthesia, which alters DA neuron activity and presynaptic function. Here we investigated the consequences of METH-induced DA terminal loss on both electrically evoked phasic-like DA signals and so-called ‘spontaneous’ RO4929097 mouse phasic DA transients measured by voltammetry in awake rats. Not ostensibly attributable to discrete stimuli, these subsecond DA changes may play a role in enhancing Enzalutamide clinical trial reward–cue associations. METH pretreatment reduced tissue

DA content in the dorsomedial striatum and nucleus accumbens by ~55%. Analysis of phasic-like DA responses elicited by reinforcing stimulation revealed that METH pretreatment decreased their amplitude and underlying mechanisms for release and uptake to a similar degree as DA content in both striatal subregions. Most importantly, characteristics of DA transients were altered by METH-induced DA terminal loss, with amplitude and frequency decreased and duration increased. These results demonstrate for the first time that denervation of DA neurons alters naturally occurring DA transients Silibinin and are consistent

with diminished phasic DA signaling as a plausible mechanism linking METH-induced striatal DA depletions and cognitive deficits. “
“Antisaccades are widely used in the study of voluntary behavioural control: a subject told to look in the opposite direction to a stimulus must suppress the automatic response of looking towards it, leading to delays and errors that are commonly believed to be generated by competing decision processes. However, currently we lack a precise model of the details of antisaccade behaviour, or indeed detailed quantitative data in the form of full reaction time distributions by which any such model could be evaluated. We measured subjects’ antisaccade latency distributions and error rates, and found that we could account precisely for both distributions and errors with a model having three competing LATER processes racing to threshold. In an even more stringent test, we manipulated subjects’ expectation of the stimulus, leading to large changes in behaviour that were nevertheless still accurately predicted. The antisaccade task is widely used in the laboratory and clinic because of the relative complexity and vulnerability of the underlying decision mechanisms: our model, grounded in detailed quantitative data, is a robust way of conceptualizing these processes.