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Opposite modulatory roles for adenosine A 1 and A 2A receptors on glutamate and dopamine release in the shell of the nucleus accumbens. Effects of chronic caffeine exposure
Author(s) -
Quarta Davide,
Ferré Sergi,
Solinas Marcello,
You ZhiBing,
Hockemeyer Jörg,
Popoli Patrizia,
Goldberg Steven R.
Publication year - 2004
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2003.02245.x
Subject(s) - nucleus accumbens , dopamine , caffeine , glutamate receptor , adenosine a2a receptor , adenosine receptor antagonist , adenosine , adenosine receptor , chemistry , pharmacology , nmda receptor , neurotransmitter , medicine , striatum , endocrinology , receptor , biology , biochemistry , agonist
Previous studies have demonstrated opposing roles for adenosine A 1 and A 2A receptors in the modulation of extracellular levels of glutamate and dopamine in the striatum. In the present study, acute systemic administration of motor‐activating doses of the A 2A receptor antagonist MSX‐3 significantly decreased extracellular levels of dopamine and glutamate in the shell of the rat nucleus accumbens (NAc) and counteracted both dopamine and glutamate release induced by systemic administration of motor‐activating doses of either the A 1 receptor antagonist CPT or caffeine. Furthermore, exposure to caffeine in the drinking water (1 mg/mL, 14 days) resulted in tolerance to the effects of systemic injection of CPT or caffeine, but not MSX‐3, on extracellular levels of dopamine and glutamate in the NAc shell. The present results show: first, the existence of opposite tonic effects of adenosine on extracellular levels of dopamine and glutamate in the shell of the NAc mediated by A 1 and A 2A receptors; second, that complete tolerance to caffeine's dopamine‐ and glutamate‐releasing effects which develops after chronic caffeine exposure is attributable to an A 1 receptor‐mediated mechanism. Development of tolerance to the dopamine‐releasing effects of caffeine in the shell of the NAc may explain its weak addictive properties and atypical psychostimulant profile.