The role of mGlu4 receptors within the nucleus accumbens in acquisition and expression of morphine-induced conditioned place preference in male rats

Abstract

Background Several studies have shown that glutamate neurotransmission in the nucleus accumbens (NAc) is required for the development of morphine-induced conditional place preference (CPP). In addition, metabotropic glutamate receptors (mGluRs) in NAc play important roles in the reward pathways. However, the precise role of mGluR4 in different steps of the morphine-induced CPP is less well known. In the present study the effect of bilateral intra-accumbal infusion of VU0155041, as a specific mGluR4 agonist on the acquisition and expression of morphine induced CPP in male Wistar rats was investigated. The animals were bilaterally implanted with guide cannulae above the NAc. In the first step of the study, the VU0155041 was administered at doses of 10, 30 and 50 μg/0.5 μL saline per side into the NAc during the 3 days of morphine (5 mg/kg) conditioning (acquisition) phase of morphine-induced CPP. In the second step of the study, the rats bilaterally received VU0155041 at the dose of 50 μg/0.5 μL, 5 min before the post-conditioning test in order to check the effect of VU0155041 on the expression of morphine-induced CPP. Results The results showed that the intra-accumbal injection of VU0155041 inhibits the acquisition of morphine-induced CPP in a dose dependent manner, but had no effect on expression. Conclusions The data indicated that intra-NAc administration of VU0155041 dose dependently blocks the establishment of morphine-induced CPP and reduces the rewarding properties of morphine. These effects may be related to changes in glutamate activity in the NAC and/or learning dependent mechanism of glutamate neurotransmission in reward pathway(s).

Effect of intrahippocampal microinjection of VU0155041, a positive allosteric modulator of mGluR4, on long term potentiation in a valproic acid-induced autistic male rat model

“…VU0155041 was microinjected through an injection needle connected to a 5-μL Hamilton microsyringe with a polyethylene tube. VU0155041 was administered into the DG over a 5-min period at concentrations of 50 μg/0.5 μl saline during the baseline recording, midway through the baseline recording session ( Ebrahimi et al, 2021 ). Control groups were administered saline.…”

Regulation and functional consequences of mGlu4 RNA editing

“…Treatment with the agonist LSP2-9166 decreased the rewarding properties of morphine and decreased reinstatement of drug seeking behavior, but this effect is suggested to be due to activation of mGlu7 due to ablation of these effects with co-administration of the mGlu7 NAM, XAP044 422 . However, intra-accumbal injection of VU0155041 was sufficient to dose dependently decrease the instatement of conditioned place preference (CPP) in a Wistar Rats 423 . Furthermore, pharmacologic activation of mGlu4 during the cessation period may help improve social functioning aspects disrupted by drug abuse and additionally may restore mGlu4 expression within the NAc 420 .…”