Effects of post-training administration of LY341495, as a mGluR2/3 antagonist on spatial memory deficit in rats fed with high-fat diet

Abstract

Background High-fat diets (HFDs) adversely influence glutamate metabolism and neurotransmission. The precise role of the group II metabotropic glutamate receptors (mGluR2/3) antagonist on spatial memory deficit following consumption of HFD has not yet been clarified. Therefore, in this study, we examined the effects of post-training administration of mGluR2/3 antagonism; LY341495 on spatial memory in rats fed with HFD by using Morris Water Maze (MWM) task. Intraperitoneal injection (i.p) injection of LY341495 was done 30 minutes before retention test. Results Our results showed that HFD did not have any effect on memory acquisition. There were not significant differences in escape latency and swimming distance between experimental groups (P>0.05, Two-way ANOVA). Our finding showed that consumption of an HFD leads to spatial memory impairment. There were significant differences in time spent in target zone between experimental groups [F (3, 20) = 7.031, P=0.0021, one-way ANOVA]. Also, LY341495 improved HFD-induced reference memory impairment. HFD animals treated with LY341495 spent more time in the target zone in compare with HFD animals (P= 0.0449). Conclusions Our results suggested that prolonged consumption of high-fat diet has no effects on the acquisition of spatial learning, but can impair memory retention of the adult male rats and post-training administration of LY341495 can improve HFD-induced reference memory impairment.

Sex differences in spatial learning and memory and hippocampal long-term potentiation at perforant pathway-dentate gyrus (PP-DG) synapses in Wistar rats

“…The MWM test, a hippocampal-dependent test, is used to assess spatial learning and memory in rodents [75][76][77][78]. The main advantage of MWM task is the distinction between spatial conditions (hidden platform) and non-spatial conditions (visible platform).…”

Are mGluR2/3 Inhibitors Potential Compounds for Novel Antidepressants?

“…Other iGluR modulators, including GluN2B-specific NMDA receptor antagonists (CP-101/ MK-0657) (Ibrahim et al 2012;Preskorn et al 2008) and NMDA receptor glycine-site partial agonists (D-cycloserine/GLYX-13) (Depression 2015; Phase), are also under various stages of clinical trials and the results appear to be acceptable to some extent. Under the encouragement of the robust antidepressant effects of ketamine, an increasing number of compounds targeting mGluRs have been tested (Cross et al 2018;Moridi et al 2020), and these compounds seem to be the most promising agents under studies for depression among the modulator of glutamatergic system (Dogra and Conn 2021). Notably, compared to other mGluRs, mGluR2/3 is a more specific target for developing novel antidepressants (Dogra and Conn 2021).…”