ADENOSINE A(2A) RECEPTOR AGONISTS INCREASE FOS-LIKE IMMUNOREACTIVITY IN MESOLIMBIC AREAS

Expression of the early-gene c-fos is an useful method for studying po tential sites of action of drugs active in the CNS. Stimulation of ade nosine A(2A) receptors by CGS 21680 (5 mg/kg) induced an increase in F os-like immunoreactivity in the rat nucleus accumbens shell, while in the rostral pole and core CGS 21680 induced Fos-like immunoreactivity only after a high dose. CGS 21680 (5 mg/kg) stimulated c-fos expressio n also in the lateral septal nucleus and dorso-medial striatum, but no t in the dorso-lateral striatum. A similar pattern of Fos-like immunor eactivity was obtained after administration of the A(2A) agonist HENEC A (5 mg/kg) which displays higher selectivity for A(2A) receptors than CGS 21680. Administration of the selective A(2A) antagonist SCH 58261 counteracted CGS 21680-induced Fos-like immunoreactivity. Lesions of the dopaminergic mesostriatal projection by 6-hydroxydopamine and stim ulation of dopamine D-2/D-3 receptors by quinpirole, prevented CGS 216 80-induced Fos-like immunoreactivity in the nucleus accumbens shell. T he present results show that stimulation of A(2A) receptors induces a profile of c-fos expression similar to that of atypical neuroleptics. A(2A) receptor stimulation has been reported to have dopamine antagoni stic actions, it is therefore suggested that A(2A) agonists might have antipsychotic activity without producing extrapyramidal side effects.