Effects of selective adenosine A 1 and A 2a agonists on amphetamine-induced locomotion and c-Fos in striatum and nucleus accumbens

Abstract

Low to moderate doses of amphetamine produce locomotion which is dependent on release of dopamine in the anteromedial striatum and nucleus accumbens. The effects of selective adenosine A 1 and A 2a receptor agonists on locomotion and c-Fos induction following a moderate dose of amphetamine was assessed in rats. Pretreatment with the adenosine A 1 receptor agonist N-6-cyclohexyladenosine (CHA) or the adenosine A 2a receptor agonist 2-[(2-aminoethylamino)carbonylethylphenylethylamino]-5′- N-ethylcarboxamidoadenosine (APEC) inhibited locomotion following an injection of amphetamine (1.5 mg/kg). This dose of amphetamine induced Fos-like immunoreactivity in an antero-dorsomedial distribution in the caudate-putamen and uniformly in the core and shell of the nucleus accumbens. Pretreatment with the adenosine A 2a receptor agonist APEC, but not the adenosine A 1 receptor agonist CHA, attenuated c-Fos induction in caudate-putamen and nucleus accumbens by amphetamine. These findings indicate that amphetamine-induced behavior is subject to modulation by adenosine receptors through mechanisms which are both related to and independent of c-Fos induction.