A role for presynaptic mechanisms in the actions of @entity7831 and XXXX .

@entity7831 @entity935 @entity7712 @entity8364 @entity1767
Psychomotor stimulants and neuroleptics exert multiple effects on dopaminergic signaling and produce the @entity935 (DA)-related behaviors of motor activation and @entity8364 , respectively. However, a clear relationship between dopaminergic activity and behavior has been very difficult to demonstrate in the awake animal, thus challenging existing notions about the mechanism of these drugs. The present study examined whether the drug-induced behaviors are linked to a presynaptic site of action, the @entity7712 ( @entity7712 ) for psychomotor stimulants and the DA autoreceptor for neuroleptics. Doses of @entity7831 (7 mg/kg i.p.), a DA uptake inhibitor, and @entity1767 (0.5 mg/kg i.p.), a dopaminergic antagonist, were selected to examine characteristic behavioral patterns for each drug: stimulant-induced motor activation in the case of @entity7831 and neuroleptic-induced @entity8364 in the case of @entity1767 . Presynaptic mechanisms were quantified in situ from extracellular DA dynamics evoked by electrical stimulation and recorded by voltammetry in the freely moving animal. In the first experiment, the maximal concentration of electrically evoked DA ([DA](max)) measured in the caudate-putamen was found to reflect the local, instantaneous change in presynaptic @entity7712 or DA autoreceptor activity according to the ascribed action of the drug injected. A positive temporal association was found between [DA](max) and motor activation following @entity7831 (r=0.99) and a negative correlation was found between [DA](max) and @entity8364 following @entity1767 (r=-0.96) in the second experiment. Taken together, the results suggest that a dopaminergic presynaptic site is a target of systemically applied psychomotor stimulants and regulates the postsynaptic action of neuroleptics during behavior. This finding was made possible by a voltammetric microprobe with millisecond temporal resolution and its use in the awake animal to assess release and uptake, two key mechanisms of dopaminergic neurotransmission. Moreover, the results indicate that presynaptic mechanisms may play a more important role in DA-behavior relationships than is currently thought.
