Chronic hyperammonemia alters motor and neurochemical responses to activation of group I metabotropic glutamate receptors in the nucleus accumbens in rats in vivo.
Hyperammonemia leads to altered cerebral function and neurological alterations in patients with hepatic encephalopathy. We studied the effects of hyperammonemia in rats on the modulation by group I metabotropic glutamate receptors (mGluR) of motor and neurochemical functions in vivo. Locomotion induced by injection of the mGluR agonist DHPG into nucleus accumbens was increased in hyperammonemic rats. In control rats DHPG increased extracellular dopamine (ca. 400%) but not glutamate. In contrast, in hyperammonemic rats DHPG increased extracellular glutamate (ca. 600%), while DHPG-induced dopamine increase was reduced. Blocking mGluR1 receptor with CPCCOEt prevented all DHPG effects, indicating that this receptor mediates its locomotor and neurochemical effects. Hyperammonemic rats showed increased (32%) mGluR1alpha, but not mGluR5 content in nucleus accumbens. These results show that modulation of locomotor and neurochemical functions by mGluRs in nucleus accumbens is strongly altered in hyperammonemia. These alterations may contribute to the neurological alterations in hyperammonemia and liver failure.
Canales
Juan-José
JJ
Laboratory of Neurobiology, Instituto de Investigaciones Citológicas, Fundación Valenciana de Investigaciones Biomédicas, Valencia, Spain.
Elayadi
Amina
A
Errami
Mohammed
M
Llansola
Marta
M
Cauli
Omar
O
Felipo
Vicente
V
D000818:Animals; D002867:Chromones / Q000494:pharmacology; D002908:Chronic Disease; D004298:Dopamine / Q000378:metabolism; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006501:Hepatic Encephalopathy / Q000378:metabolism* / Q000503:physiopathology; D022124:Hyperammonemia / Q000378:metabolism* / Q000503:physiopathology; D007150:Immunohistochemistry; D017551:Microdialysis; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects / Q000378:metabolism*; D012118:Resorcinols / Q000494:pharmacology
C117789:7-(hydroxyimino)cyclopropan(b)chromen-1a-carbxoylic acid ethyl ester; D002867:Chromones; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; C578937:Grm5 protein, rat; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D012118:Resorcinols; C104077:metabotropic glutamate receptor type 1; D018698:Glutamic Acid; C079215:3,5-dihydroxyphenylglycine; D005998:Glycine; D004298:Dopamine