Stimulation of metabotropic but not ionotropic glutamatergic receptors in the nucleus accumbens is required for the D-amphetamine-induced release of functional dopamine

We have previously shown that a large part of the D-amphetamine-induced rel ease of dopamine in the nucleus accumbens is not associated with an increas e in locomotor activity, and that "functional" dopamine release (i.e. relea se of dopamine associated with locomotor activity) requires the distal faci litation of noradrenergic transmission through alpha1-adrenergic receptors in the prefrontal cortex. To determine the role of monosynaptic or polysyna ptic projections from the prefrontal cortex to the nucleus accumbens in the se amphetamine responses, either AMPA/kainate (6-cyano-7-nitroquinoxaline-2 ,3-dione, CNQX, 300 muM), N-methyl-D-aspartate (D(-)-2-amino-5-phosphono-pe ntanoic acid, APV, 500 muM) or metabotropic [(+)-alpha -methyl-4-carboxy-ph enylglycine, MCPG, 10 mM] glutamate receptor antagonists were infused throu gh a dialysis probe in the rat nucleus accumbens. CNQX and MCPG but not APV reduced the "non-functional" release of dopamine evoked by local (3 muM) a nd systemic D-amphetamine (2 mg/kg i.p.) treatments. However, the locomotor hyperactivity and functional dopamine release induced by systemic D-amphet amine were abolished by MCPG, but neither by CNQX nor by APV. MCPG treatmen t also abolished the hyperlocomotor activity and functional dopamine releas e evoked by bilateral morphine injection into the ventral tegmental area. T he dopamine release evoked by this morphine treatment was 16-fold lower tha n that induced by the systemic D-amphetamine injection, although similar be havioral activations were observed. Altogether, our results further aid the discrimination of functional and no n-functional release of dopamine. We suggest that the activation of metabot ropic glutamate receptors in the nucleus accumbens is required for function al dopamine release following systemic D-amphetamine injection. (C) 2001 IB RO, Published by Elsevier Science Ltd. All rights reserved.