Molecular cloning of the rat A2 adenosine receptor: selective co-expression with D2 dopamine receptors in rat striatum

Simultaneous Blockade of Adenosine A2A and Metabotropic Glutamate mGlu5 Receptors Increase their Efficacy in Reversing Parkinsonian Deficits in Rats

“…In contrast to the widespread distribution of other adenosine receptor subtypes (A 1 , A 2B , and A 3 ), the A 2A receptor subtypes shows a quite specific localization in the basal ganglia largely restricted to the striatum (Svenningsson et al, 1999;Fredholm et al, 2001). As shown by in situ hybridization and binding studies (Martinez-Mir et al, 1991;Schiffmann et al, 1991;Svenningsson et al, 1998), the A 2A receptor is coexpressed with DA D 2 receptors in the striatopallidal GABAergic neurons, which contain enkephalin and originate in the so-called striatal efferent indirect pathway (Fink et al, 1992). Behavioral data support the strong A 2A -D 2 receptor interactions to explain the enhancement of the antiParkinsonian effects of DA agonists in rodent models of PD (Pinna et al, 1996;Fenu et al, 1997;Koga et al, 2000;Hauber et al, 2001).…”

“…In addition, group I mGlu receptors are present in the subthalamic nucleus (STN) and the substantia nigra pars reticulata (SNr) (Tallaksen-Greene et al, 1998;Testa et al, 1994). In the striatum, adenosine A 2A receptors are predominantly expressed by g-amino butyric acid (GABA)-enkephalin striatopallidal neurons, where they colocalize with DA D 2 receptors (Fink et al, 1992;MartinezMir et al, 1991) and are also present in 25% of cholinergic interneurons (Schiffmann et al, 1991;Fredholm et al, 2001). Interestingly, mGlu 5 receptors show a striking similar localization in the striatopallidal GABAergic projection neurons and interneurons in primates , so providing a morphological basis for the possible existence of functional interactions between striatal A 2A and mGlu 5 receptors.…”

Intra-accumbens injections of the adenosine A2A agonist CGS 21680 affect effort-related choice behavior in rats

“…Although there are at least four types of adenosine receptors, adenosine A 2A receptors are primarily localized in striatal areas, including both neostriatum and nucleus accumbens (Jarvis and Williams 1989;Schiffmann et al 1991;DeMet and Chicz-DeMet 2002;Ferré et al 2004). In these striatal areas, there is considerable evidence of a functional interaction between dopamine D 2 and adenosine A 2A receptors (Fink et al 1992;Ferré 1997;Hillion et al 2002;Fuxe et al 2003). This interaction has typically been investigated in connection with neostriatal motor functions that are potentially related to parkinsonism Svenningsson et al 1999;Ferré et al 2001;Hauber et al 2001;Morelli and Pinna 2002;Jenner 2003Jenner , 2005Pinna et al 2005).…”

Adenosine A2A Receptor Antagonists and Parkinson’s Disease

“…In the striatum adenosine A 2A receptors colocalize and physically associate with dopamine D 2 receptors. 2 14 animals and dramatic relief of parkinsonian symptoms in MPTPtreated 15 nonhuman primates. 16 A 2A antagonists facilitate dopamine receptor signaling and thereby normalize motor function in animal models of dopamine dysregulation.…”

“…The majority of motor impairments of PD are caused by a gradual loss of dopamine (DA) producing neurons in the ventral midbrain and concomitant loss of DA input to forebrain (striatal) motor structures. 2,3 The loss of DA input to the neostriatum leads to dysregulation of striatal function and the classic motor symptoms of PD, such as resting tremor, muscular rigidity, and bradykinesia.The majority of treatments aim to restore dopamine signaling and thereby reduce the severity of the motor symptoms. Dopamine replacement therapy using L-DOPA, the precursor to dopamine, remains the gold-standard treatment for PD.…”