Differential modulation of the D1-like- and D2-like dopamine receptor-induced locomotor responses by group II metabotropic glutamate receptors in the rat nucleus accumbens.
There is strong evidence for the existence of functional interactions between metabotropic glutamate receptors and dopamine transmission in the nucleus accumbens. In the present study, we investigated the interactions between group II mGlu receptors and D1-like- and D2-like receptors in the rat nucleus accumbens. Administration of the selective group II metabotropic glutamate receptor agonist APDC, which had no effect when injected alone, potentiated the locomotor response produced by the selective D1-like receptor agonist SKF 38393 but had no effect on those induced by the selective D2-like receptor agonist quinpirole (also known as LY 171555)--a compound believed to act only at D2-like presynaptic receptors when injected alone--or co-administration of SKF 38393+quinpirole--a pharmacological condition thought to stimulate both D1-like receptors and presynaptic and postsynaptic D2-like receptors. In contrast, the selective group II mGlu receptor antagonist LY 341495, which induced an increase in basal locomotor activity, showed no effect on the SKF 38393-induced locomotor response, but abolished that produced by quinpirole or SKF 38393+quinpirole. The present findings demonstrate that stimulation of group II mGlu receptors has a cooperative and potentiating action on the locomotor response induced by D1-like receptor activation, whereas blockade of group II mGlu receptors has an antagonist action on the locomotor responses induced by activation of D2-like receptors. Although these data are consistent from a pharmacological point of view, as the effects of the group II mGlu receptor antagonist LY 341495 were blocked by the group II mGlu receptor agonist APDC and conversely, the subtle neurochemical crosstalks underlying such a differential effect of group II mGlu receptors on D1-like- and D2-like DA receptors remain to be elucidated.
David
H N
HN
UMR CNRS 6551, Centre Cyceron, BP5229, Université de Caen, Boulevard H. Becquerel, 14074 Caen cedex, France.
Abraini
J H
JH
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D018491:Dopamine Agonists / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009714:Nucleus Accumbens / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D011392:Proline / Q000031:analogs & derivatives / Q000494:pharmacology; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000187:drug effects*; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects*; D014966:Xanthenes / Q000494:pharmacology
C097299:4-aminopyrrolidine-2,4-dicarboxylic acid; D000596:Amino Acids; D018491:Dopamine Agonists; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; C114624:LY 341495; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D018094:Receptors, Metabotropic Glutamate; D014966:Xanthenes; D019257:Quinpirole; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D011392:Proline