Abstract
BackgroundSeveral 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.ResultsThe 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.ConclusionsThe 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).
Highlights
Several studies have shown that glutamate neurotransmission in the nucleus accumbens (NAc) is required for the development of morphine-induced conditional place preference (CPP)
Effects of intra‐accumbal microinjection of mGluR4 receptor agonist, VU0155041, on the acquisition of morphine‐induced conditioned place preference (CPP) To investigate the effects of mGluR4 agonist on the acquisition of morphine-induced CPP, intra-accumbal injection of VU0155041 (10, 30 and 50 μg/0.5 μL) was bilaterally done 5 min prior to each morphine injection during the 3-day conditioning phase (Fig. 1)
The findings revealed that there is no significant difference between the conditioning score (CS) in the anatomical control (223.6 ± 17.6) and vehicle group (227.5 ± 35)
Summary
Several studies have shown that glutamate neurotransmission in the nucleus accumbens (NAc) is required for the development of morphine-induced conditional place preference (CPP). Metabotropic glutamate receptors (mGluRs) in NAc play important roles in the reward pathways. 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. Anatomical and electrophysiological studies have shed light on the fact that glutamatergic input into the NAc originating from the medial prefrontal cortex, VTA, and amygdala play an important role in addictive behaviors [8, 9]. Glutamate inputs into the NAc are involved in conditioned place preference (CPP) induced by morphine, cocaine, or amphetamine [10]. Disrupted synaptic plasticity in the NAc following chronic exposure to several classes of drugs of abuse, allows drug-associated cues to engender a pathologic motivation for drug seeking [10]
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