Role of group II metabotropic glutamate receptors (mGluR2/3) blockade on long-term potentiation in the dentate gyrus region of hippocampus in rats fed with high-fat diet

Abstract

In the hippocampus, metabotropic glutamate receptors (mGluRs) are involved in various forms of synaptic plasticity. High-fat diets (HFDs) adversely influence hippocampal structure and function and induce changes in hippocampal glutamate metabolism and neurotransmission. Here, we studied the induction of hippocampal long-term potentiation (LTP) while blocking group II mGluR2/3. Thirty-two male Wistar rats were assigned into four groups: a control group that consumed an ordinary diet; a HFD group that ate a HFD; "HFD plus LY341495" ate a HFD and later received a selective group II metabotropic glutamate receptor antagonist; and "Control plus LY341495" group. After 6 months on the specified diet, the rats were anesthetized with intraperitoneal injection of ketamine and xylazin, and placed in a stereotaxic apparatus for surgery, electrode implantation, and field potential recording. We microinjected LY341495 solution unilaterally into the dentate gyrus (DG) to block mGluR2/3. The population spike (PS) amplitude and slope of excitatory post synaptic potentials (EPSP) were measured in the DG area in response to stimulation applied to the perforant pathway (400 Hz tetanization). We found that, after tentanizing the perforant pathway to induce LTP, HFD decreased PS amplitude and slope of EPSP compared to controls. Moreover, blocking group II mGluRs increased LTP not only in controls, but also in rats fed on HFD. Therefore, our results show that LY341495 rescues hippocampal synaptic plasticity that can be impaired by a HFD. In summary, these results indicate that mGluR2/3 inhibition may have stimulatory effects on LTP induction in the DG.