Altered modulation of motor activity by group I metabotropic glutamate receptors in the nucleus accumbens in hyperammonemic rats.

摘要

One of the neurological complications in hepatic encephalopathy is the impairment of motor coordination and function. Clinical signs of basal ganglia, cortico-spinal and cerebellar dysfunction have been commonly detected in these patients. We are studying the molecular bases of the alterations in motor coordination and function in hepatic encephalopathy. Hyperammonemia is considered the main factor responsible for the neurological alterations in patients with hepatic encephalopathy. Activation of metabotropic glutamate receptors (mGluRs) in the nucleus accumbens (NAcc) induces locomotion in rats. Asa first step in our studies on the alterations in motor co-ordination and function in hyperammonemia and hepatic encephalopathy we studied whether the control of motor function by mGluRs in the NAcc is altered in hyperammonemic rats. The locomotor activity induced by injection into the nucleus accumbens (NAcc) of DHPG, an agonist of group I mGluRs was significantly increased in hyperammonemic rats. Injectionof DHPG increased extracellular dopamine but not glutamate in the NAcc of control rats. In hyperammonemic rats DHPG-induced increase in dopamine was significantly reduced, and extracellular glutamate increased 6-fold. The content of mGluR 1 but not mGluR 5, is increased in the NAcc of hyperammonemic rats. Blockade of mGluR 1 completely prevented motor and neurochemical effects induced by DHPG. These results show that modulation of both motor function and extracellular concentration of neurotransmitters by mGluRs in the NAcc is altered in hyperammonemia. This may contribute to the alterations in motor function in hepatic encephalopathy.