Striatum dopaminergic transmission

In this regard, considerable evidence shows that PCP increases dopaminergic transmission in the striatum (Johnson 1983) and, more recently, evidence indicates that DA function is increased in the mesolimbic and mesocortical pathways as well. For example, PCP administration has been shown to inhibit the firing of cells found in the ventral tegmental area (Freeman and Bunney 1984) similar to that observed in the substantia nigra (Raja and Guyenet 1980). 

Garris, P. A. and Wightman, R. M. Different kinetics govern dopaminergic transmission in the amygdala, prefrontal cortex, and striatum an in vivo voltammetric study. /. Neurosci. 14 442-450,1994. 

Dopamine receptor agonists. Deficient dopaminergic transmission in the striatum can be compensated by ergot derivatives (bromocriptine p. 114], lisu-ride, cabergoline, and pergolide) and nonergot compounds (ropinirole, prami-pexole). These agonists stimulate dopamine receptors (D2, D3, and D sub-types), have lower clinical efficacy than levodopa, and share its main adverse effects. 

Barrot M, Abrous DN, Marinelli M, Rouge-Pont F, Le MM, et al. 2001. Influence of glucocorticoids on dopaminergic transmission in the rat dorsolateral striatum. Eur J Neurosci 13 812-818. 

Gonon F, Burie JF, Jaber M, Benoit-Marand M, Diumartin B, Bloch B (2000) Geometry and kinetics of dopaminergic transmission in the rat striatum and in mice lacking the dopamine transporter. Prog Brain Res 125 291-302. 

Ultrastructural characterization of the D2 receptors have revealed that they are often present within the GABA-containing cells within the striatum, cerebral cortex, hippocampus, globus pallidus and thalamic reticular nucleus (Mrzljak et al., 1996). Thus, dopaminergic transmission via the D2 receptors predominantly provides inhibitory local intrinsic control in the cerebral cortex and inhibitory regulation of the projection pathways. 

These results confirm that ciclosporin can modulate dopaminergic transmission in the striatum, presumably by inhibition of calcineurin. 

In both male and female rats, the neurobehavioral NOEL was 2 mg kg based on hyperactivity and increased motor activity. Triadimefon has been shown to increase motor activity and stereotyped response in a manner resembling psychomotor stimulants by potentiation of dopaminergic transmission. One study noted enhanced locomotor and stereotypic behavioral patterns in Sprague-Dawley rats treated with repeated triadimefon exposure (100 mg kg every other day for 14 days). Eurther-more, this study suggested that chronic exposure to triadimefon may involve effects of dopamine uptake in the striatum and nucleus accumbens. 

The symptomatic action of MAO-B inhibitors is mediated by blockade of the MAO-B enzyme involved in dopamine degradation, which results in increased dopamine availability at the synapse. This is not, however, the only mechanism of action. The symptomatic effect is also mediated by inhibition of amine uptake and a major increase in phenylethylamine concentrations in the striatum. Phenylethylamine is a trace amine which can amplify dopaminergic transmission. In addition, it has been proposed that blocking MAO-B metabolism of N-acetylated polyamine derivatives could modulate the activity of inhibitor glutamatergic efferents at the subthalamic level. The exact role of selegiline in amphetamine metabolism is not clearly understood. 

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