RESUMO
Numerous findings confirm that the metabotropic glutamate receptors (mGluRs) are involved in the conditioned place preference (CPP) induced by morphine. Here we focused on the role of mGluR5 in the nucleus accumbens (NAc) as a main site of glutamate action on the rewarding effects of morphine. Firstly, we investigated the effects of intra-NAc administrating mGluR5 antagonist 3-((2-Methyl-1,3-thiazol-4-yl) ethynyl) pyridine hydrochloride (MTEP; 1, 3, and 10 µg/µl saline) on the extinction and the reinstatement phase of morphine CPP. Moreover, to determine the downstream signaling cascades of mGluR5 in morphine CPP, the protein levels of stromal interaction molecules (STIM1 and 2) in the NAc and hippocampus (HPC) were measured by western blotting. The behavioral data indicated that the mGluR5 blockade by MTEP at the high doses of 3 and 10 µg facilitated the extinction of morphine-induced CPP and attenuated the reinstatement to morphine in extinguished rats. Molecular results showed that the morphine led to increased levels of STIM proteins in the HPC and increased the level of STIM1 without affecting STIM2 in the NAc. Furthermore, intra-NAc microinjection of MTEP (10 µg) in the reinstatement phase decreased STIM1 in the NAc and HPC and reduced the STIM2 in the HPC. Collectively, our data show that morphine could facilitate brain reward function in part by increasing glutamate-mediated transmission through activation of mGluR5 and modulation of STIM proteins. Therefore, these results highlight the therapeutic potential of mGluR5 antagonists in morphine use disorder.
RESUMO
The role of the anterior thalamic nuclei (ATN) has been proven in different learning and memory tasks. The ATN consist of three main subnuclei, the anterodorsal (AD), anteroventral (AV) and anteromedial (AM), which have different biological characteristics such as distinct circuitry, cell population and neurotransmitter content. The role of ATN subnuclei in learning and memory has been shown in several studies. However, their probable role in different phases of memory including acquisition, consolidation and retrieval are not still well-known. For this purpose, the effect of reversible inactivation of each ATN subnucleus on different memory phases in two behavioral tasks including passive avoidance (PA) and Morris water maze (MWM) was studied. Wister male rats were bilaterally implanted with cannulas above the AD, AV or AM subnucleus in separate experimental groups in order to inject lidocaine (4%) for their temporal inactivation or, equal volume of saline. Animals were trained in the behavioral tasks and different phases of memory were investigated. Our findings indicated that the AV inactivation strongly disrupts all memory phases in the MWM, and consolidation and retrieval phases in the PA tasks. The AM inactivation had no effect on acquisition of both tasks while it impaired the PA consolidation and MWM retrieval. However, the AD inactivation could not disrupt memory phases in the PA task but impaired the MWM retrieval. In conclusion, it seems that the ATN distinct subnuclei differently affect different phases of memory in these two tasks.
