Effects of Group II Metabotropic Glutamate Receptor Modulation on Ethanol- and Sucrose-Seeking and Consumption in the Rat

Rationale Previous studies suggest that group II metabotropic glutamate receptors (mGluR2/3) are involved in regulating ethanol seeking and consumption. Objective The mGluR2/3 agonist LY379268 (LY37) and selective mGluR2 positive allosteric modulator biphenyl-indanone A (BINA) were used to investigate the relative contribution of mGlu2 and mGlu3 receptors on ethanol and sucrose seeking and consumption. A microinjection study was then performed to examine the role of nucleus accumbens (NAc) core mGluR2/3 on ethanol-seeking. Methods For the systemic experiments, separate groups of male Wistar rats [LY37 (0-2.0 mg/kg); BINA (0-20 mg/kg)] were trained to complete a response requirement (RR) resulting in access to 10% ethanol or 2% sucrose (in separate groups) for a 20-minute drinking period. Animals then underwent consummatory testing (weekly drug injections with RR1) followed by appetitive testing (weekly drug injections followed by extinction session). A separate group of male Wistar rats was surgically implanted with bilateral guide cannulae directed towards the NAc core and had weekly microinjections followed by an extinction session. Results Systemic administration of the mGluR2/3 agonist LY37 significantly reduced ethanol- and sucrose-seeking. The same treatment also reduced sucrose consumption and body weight (24-hours post injection). Systemic administration of the selective mGluR2 PAM BINA, however, had no effect on either seeking or consumption of ethanol or sucrose. Intra-accumbens core LY37 significantly reduced ethanol-seeking. Conclusions: These findings suggest that systemic mGluR2/3 agonism, but not allosteric modulation of mGluR2, reduces reinforcer seeking. In particular, NAc core group II mGluR may be involved in regulating ethanol-seeking