Distribution of adenosine A2A receptor antagonist KW-6002 and its effect on gene expression in the rat brain

Cocaine-induced sensitization is associated with altered dynamics of transcriptional responses of the dopamine transporter, tyrosine hydroxylase, and dopamine D2 receptors in C57Bl/6J mice

“…Our group and others have previously reported fast regulation of mRNA levels of genes coding for neuropeptides and neurotransmitter receptors in the striatum (Aoyama et al 2002;Izawa et al 2006;Zhou et al 2002). These rapid changes in mRNA levels can also be attributable to changes in mRNA stability/availability and not necessarily to changes in gene expression.…”

Stimulation of Adenosine Receptors Selectively Activates Gene Expression in Striatal Enkephalinergic Neurons

“…By means of the strong antagonistic D 2 -A 2A receptor interaction at the adenylyl cyclase level, and due to the existence of a tonic effect of dopamine on D 2 receptors, under normal conditions A 2A receptors are practically unable to activate the cAMP-PKA signaling pathway (Agnati et al, 2003;Ferré et al, 2003Ferré et al, , 2004. In fact, the systemic administration of A 2A receptor antagonists produces either no effect or a modest decrease in the striatal expression of c-fos or preproenkephalin (Le Moine et al, 1997;Pinna et al, 1997;Aoyama et al, 2002;Carta et al, 2002;Karcz-Kubicha et al, 2003;Wardas et al, 2003). It must also be pointed out that some studies suggest that A 2A and D 2 receptor can interact synergistically, with stimulation of D 2 receptors potentiating the effects of A 2A receptor stimulation.…”

The effect of the adenosine A2A antagonist KW-6002 on motor and motivational processes in the rat

“…Since in the rat it has been shown that motor preparatory processes are mediated by prefrontal-cortical areas (Risterucci et al 2003) and dopaminergic transmission in the striatum (Baunez et al 1995;Brown and Robbins 1991), it is likely that motor preparation is subserved by the parallel cortico-striatal circuitry (see Alexander and Crutcher 1990;Mink 1996) and that KW-6002, which is distributed to both cortical and striatal areas following oral administration (Aoyama et al 2002), impinges on this system. Whether the effects of KW-6002 on anticipatory responses observed in this study are due to an enhancement of temporal probability summation or an influence on time estimation processes remains to be seen.…”

“…The order of doses was counterbalanced such that any effect of dose could not be due to an effect of day. Orally administered KW-6002 has been shown to reach peak levels in rat brain at 30 min, which is maintained for 60 min at the low dose employed here (Aoyama et al 2002). Therefore, the testing sessions were initiated at 60 min following drug administration, and all sessions were completed or terminated after 30 min.…”