title: Enabling role of adenosine A1 receptors in adenosine A2A receptor-mediated striatal expression of c-fos.
abstract: When striatal neurons are strongly activated they produce adenosine, which activates nearby adenosine A1 receptors (A1Rs) and adenosine A2A receptors (A2ARs). Although the effects of A1R or A2AR activation on neural activity in the striatum have been examined separately, the effects of coactivating both receptors has not been investigated. Using c-Fos immunohistochemistry as an indicator of neural activity, we examined the effects of coactivation of A1Rs and A2ARs on neural activity and their mechanism of interaction in the caudate-putamen, nucleus accumbens (NAc) and prefrontal cortex in rats. Administration of a motor-depressant dose of the A2AR agonist CGS 21680 (0.5 mg/kg i.p.) did not significantly induce c-fos expression in any of these brain regions. Administration of a motor-depressant dose of the A1R agonist CPA (0.3 mg/kg, i.p.) produced a small but significant induction of c-fos expression only in the shell of the NAc. Coadministration of CGS 21680 and CPA produced a synergistic induction of c-fos expression in the caudate-putamen, cingulate cortex, and especially the NAc. In the shell of the NAc administration of CPA significantly decreased extracellular dopamine levels measured by in vivo microdialysis and blocked CGS 21680-induced increases in dopamine levels. Because it has been previously shown that activation of dopamine D2 receptors (D2Rs) by endogenous dopamine blocks A2AR-mediated c-fos expression, it is hypothesized that the enabling role of A1Rs in A2AR-mediated striatal c-fos expression is related to the A1R-mediated inhibition of dopamine release.
authors.affiliation: Preclinical Pharmacology Section, Department of Health and Human Services, NIH, NIDA, IRP, Baltimore MD 21224, USA.
authors.forename: Marzena
authors.initials: M
authors.lastname: Karcz-Kubicha
authors.forename: Davide
authors.initials: D
authors.lastname: Quarta
authors.forename: Bruce T
authors.initials: BT
authors.lastname: Hope
authors.forename: Katerina
authors.initials: K
authors.lastname: Antoniou
authors.forename: Christa E
authors.initials: CE
authors.lastname: Müller
authors.forename: Marisela
authors.initials: M
authors.lastname: Morales
authors.forename: Charles W
authors.initials: CW
authors.lastname: Schindler
authors.forename: Steven R
authors.initials: SR
authors.lastname: Goldberg
authors.forename: Sergi
authors.initials: S
authors.lastname: Ferré
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000032:analysis; D004357:Drug Synergism; D007150:Immunohistochemistry; D008297:Male; D017551:Microdialysis; D009474:Neurons / Q000378:metabolism*; D010627:Phenethylamines / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis* / Q000187:drug effects; D058906:Purinergic P1 Receptor Agonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1 / Q000378:metabolism*
chemical_list: D010627:Phenethylamines; D016760:Proto-Oncogene Proteins c-fos; D058906:Purinergic P1 Receptor Agonists; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; C048599:N(6)-cyclopentyladenosine; D000241:Adenosine; D004298:Dopamine