Stimulation of group I mGlu receptors in the ventrotegmental area enhances extracellular dopamine in the rat medial prefrontal cortex

Abstract

Group I mGlu receptors have been implicated in the control of brain dopamine release. However, the receptor subtype involved and the precise site of action have not been determined. In this study we show that (R,S)3,5-dihydroxyphenylglycine (DHPG; 6 and 60 nmol ICV), a selective group I mGlu receptor agonist, raised extracellular dopamine respectively by 176% and 243% of basal values in the medial prefrontal cortex as assessed by in vivo microdialysis in conscious rats. (R,S)2-chloro-5-hydroxyphenylglycine (60 nmol ICV), a selective mGlu5 receptor agonist, raised extracellular dopamine by 396% of basal values. Intra-VTA DHPG (0.6-6 nmol) mimicked ICV injection whereas intracortical infusion (1-1000 lmol/L) had no effect. DHPG-induced rise of extracellular dopamine was reversed by tetrodotoxin and by the selective mGlu1 and mGlu5 receptor antagonists 7(hydroxyimino)cyclopropa [b]chromen-1a-carboxylate (CPCCOEt) and 2-methyl-6-(phenylethynyl)pyridine (MPEP) either ICV or into the ventrotegmental area (VTA), suggesting that neuronal release and both mGlu1 and mGlu5 receptors were involved. These results support the existence of functional mGlu1 and mGlu5 receptors in the VTA regulating the release of dopamine in the medial prefrontal cortex. Keywords: 2-methyl-6-(phenylethynyl)pyridine, 7(hydroxyimino)cyclopropa[b]chromen-1a-carboxylate, (R,S)3,5-dihydroxyphenylglycine, dopamine, medial prefrontal cortex, mGlu1 and mGlu5 receptors, ventrotegmental area.

Dissociable roles of mGlu5 and dopamine receptors in the rewarding and sensitizing properties of morphine and cocaine

“…Mesolimbic dopamine has been widely implicated in the rewarding effects of drugs of abuse (Koob et al 1998; Wise 2004; Pierce and Kumaresan 2006), but it does not play a critical role in the development of sensitization of the psychomotor stimulant properties of cocaine and morphine (Vanderschuren and Kalivas 2000). Furthermore, it has been shown that mGlu5 receptor stimulation can raise extracellular dopamine in prefrontal cortex and striatum, which can be blocked by, for instance, MPEP or the general mGluR antagonist (+)-MCPG (Bruton et al 1999; Renoldi et al 2007). Thus, mGlu5 receptor blockade may reduce the ability of cocaine or morphine to enhance mesolimbic dopamine neurotransmission which may, in turn, attenuate the rewarding effects of these drugs—although cocaine did increase nucleus accumbens dopamine overflow in mGlu5 receptor knockout mice (Chiamulera et al 2001).…”

Glutamatergic transmission is involved in the long lasting sexual inhibition of sexually exhausted male rats

“…In addition, AMPA/kainate receptor activity plays a role in regulating dopamine release (Desce et al, 1991), while mGluR5 receptors of the VTA regulate the release of this neurotransmitter in the medial prefrontal cortex (Renoldi et al, 2007) and the selective non-competitive mGluR5 antagonist MPEP elevates NAcc dopamine levels (Chau et al, 2011).…”

Acamprosate-responsive brain sites for suppression of ethanol intake and preference

“…Further, antagonism of NMDA receptors within the VTA has also been shown to reduce reward-seeking behaviors (31). Finally, acamprosate reduces behavioral ethanol withdrawal (2,55), ameliorates glutamate neurotoxicity, and therefore, may limit the drive to drink (15,28,35) by acting in part through metabotropic glutamate type 5 receptors (mGlu5) (28,38), which are also present in the VTA (46).…”