| Stimulation of group I and group II metabotropic glutamate receptors (mGluR) in the rat nucleus accumbens (NA) and ventral tegmental area elicits locomotor activity. Locomotor activation produced by group I mGluR stimulation in the NA is dependent upon mGluR1 but not mGluR5. Furthermore, this effect is abolished by blockade of AMPA-type glutamate receptors. Reverse microdialysis of the group I selective agonist (3,5)-dihydroxyphenylglycine (DHPG) into the NA results in an increase in extracellular glutamate levels. Similar to the pharmacology of the behavioral activation, this response is dependent upon mGluR1 stimulation but not mGluR5. Moreover, the DHPG-induced rise in extracellular glutamate is blocked by the Na+ channel blocker tetrodotoxin and the N-type Ca2+ channel antagonist o-conotoxin. Following 3 weeks withdrawal from repeated cocaine administration, both the locomotor activation and rise in extracellular glutamate produced by DHPG in the NA are significantly attenuated. These findings may be attributed to a reduction in the group I mGluR-associated scaffolding protein Homer 1 b/c in the meidal NA following withdrawal from cocaine administration. Repeated cocaine administration does not alter phospholipase C-beta1 protein levels or DHPG-stimulated phospholipase C-beta1 activity in the NA. |
