Adenosine receptor‐mediated modulation of dopamine release in the nucleus accumbens depends on glutamate neurotransmission and N‐methyl‐d‐aspartate receptor stimulation

Abstract

Adenosine, by acting on adenosine A 1 and A 2A receptors, exerts opposite modulatory roles on striatal extracellular levels of glutamate and dopamine, with activation of A 1 inhibiting and activation of A 2A receptors stimulating glutamate and dopamine release. Adenosine-mediated modulation of striatal dopaminergic neurotransmission could be secondary to changes in glutamate neurotransmission, in view of evidence for a preferential colocalization of A 1 and A 2A receptors in glutamatergic nerve terminals. By using in vivo microdialysis techniques, local perfusion of NMDA (3, 10 lM), the selective A 2A receptor agonist 2-p-(2-carboxyethyl)phenethylamino-5¢-N-ethylcarboxamidoadenosine (CGS 21680; 3, 10 lM), the selective A 1 receptor antagonist 8-cyclopentyl-1,3-dimethylxanthine (CPT; 300, 1000 lM), or the non-selective A 1 -A 2A receptor antagonist in vitro caffeine (300, 1000 lM) elicited significant increases in extracellular levels of dopamine in the shell of the nucleus accumbens (NAc). Significant glutamate release was also observed with local perfusion of CGS 21680, CPT and caffeine, but not NMDA. Co-perfusion with the competitive NMDA receptor antagonist DL-2-amino-5-phosphonovaleric acid (APV; 100 lM) counteracted dopamine release induced by NMDA, CGS 21680, CPT and caffeine. Co-perfusion with the selective A 2A receptor antagonist MSX-3 (1 lM) counteracted dopamine and glutamate release induced by CGS 21680, CPT and caffeine and did not modify dopamine release induced by NMDA. These results indicate that modulation of dopamine release in the shell of the NAc by A 1 and A 2A receptors is mostly secondary to their opposite modulatory role on glutamatergic neurotransmission and depends on stimulation of NMDA receptors. Furthermore, these results underscore the role of A 1 vs. A 2A receptor antagonism in the central effects of caffeine.

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

“…Therefore, this local-circuit mechanism can explain why activation of adenosine A 1 receptors allows A 2A receptors to overcome the inhibitory effect of D 2 receptors and induce striatal expression of c-fos and preproenkephalin. We have recently studied the mechanisms involved in the A 2A receptor-mediated striatal dopamine release and suggested that it depends on glutamate neurotransmission (facilitation of glutamate release by the stimulation of A 2A receptor localized in striatal glutamatergic terminals) and NMDA receptor stimulation (facilitation of dopamine release by spillover of glutamate and stimulation of NMDA receptors localized in dopaminergic terminals) (Quarta et al, 2004). Concomitant administration of an A 1 receptor agonist counteracts CGS 21680-induced dopamine release (Karcz-Kubicha et al, 2003) most probably by indirect inhibitory effects on glutamate release (Quarta et al, 2004) and direct inhibitory effects on dopamine release (Borycz et al, in preparation).…”

“…We have recently studied the mechanisms involved in the A 2A receptor-mediated striatal dopamine release and suggested that it depends on glutamate neurotransmission (facilitation of glutamate release by the stimulation of A 2A receptor localized in striatal glutamatergic terminals) and NMDA receptor stimulation (facilitation of dopamine release by spillover of glutamate and stimulation of NMDA receptors localized in dopaminergic terminals) (Quarta et al, 2004). Concomitant administration of an A 1 receptor agonist counteracts CGS 21680-induced dopamine release (Karcz-Kubicha et al, 2003) most probably by indirect inhibitory effects on glutamate release (Quarta et al, 2004) and direct inhibitory effects on dopamine release (Borycz et al, in preparation). Whatever the mechanisms involved, concomitant A 1 receptor stimulation, which is actually what occurs with endogenous adenosine release, enables A 2A receptor stimulation to produce a significant increase in the striatal expression of c-fos and preproenkephalin.…”

Adenosine A2A receptors in ventral striatum, hypothalamus and nociceptive circuitry

“…However, these effects of caffeine appear to be due to A 1 rather than A 2A receptor blockade (Kuzmin et al, 1999;Green and Schenk, 2002, Solinas et al, 2002, 2005Karcz-Kubicha et al, 2003;Quarta et al, 2004Quarta et al, 2005Antoniou et al, 2005). Thus, caffeine and selective A 1 receptor antagonists have many behavioral, subjective and biochemical similarities to other psychostimulants, including their ability to induce dopamine release in the nucleus accumbens (Solinas et al, 2002(Solinas et al, , 2005Karcz-Kubicha et al, 2003;Quarta et al, 2004aQuarta et al, , 2004bAntoniou et al, 2005). Nevertheless, we should distinguish between acute and chronic caffeine treatment.…”

“…Nevertheless, we should distinguish between acute and chronic caffeine treatment. We recently demonstrated that A 1 receptor antagonism plays a key role in the acute motor-activating, discriminative stimulus and dopamine-releasing effects of systemically administered caffeine in rats (Solinas et al, 2002(Solinas et al, , 2005Karcz-Kubicha et al, 2003;Quarta et al, 2004aQuarta et al, , 2004bAntoniou et al, 2005). However, the A 1 receptor antagonistic effects disappear with chronic treatment with caffeine, while A 2A receptor antagonistic effects remain (Karcz-Kubicha et al, 2003;Quarta et al, 2004a).…”

Fluctuations in Endogenous Kynurenic Acid Control Hippocampal Glutamate and Memory

“…Briefly, KYNA was measured following isocratic elution with a mobile phase containing 200 mM zinc acetate and 5% acetonitrile (pH 6.2), and detected fluorimetrically (excitation wavelength: 344 nm; emission wavelength: 398) (Shibata, 1988). Glutamate (o-phthalaldehyde/2-mercaptoethanol derivatization; excitation wavelength: 390 nm; emission wavelength: 460 nm) was determined fluorimetrically after gradient elution (Quarta et al, 2004).…”