Hyperammonaemia alters the mechanisms by which metabotropic glutamate receptors in nucleus accumbens modulate motor function.
Activation of metabotropic glutamate receptors by injecting (S)3,5-dihydroxyphenylglycine (DHPG) in nucleus accumbens (NAcc) increases motor activity by different mechanisms in control rats and in rats with chronic liver failure due to portacaval shunt. In control rats DHPG increases extracellular dopamine in NAcc and induces locomotion by activating the 'normal' circuit: NAcc-->ventral pallidum-->medial-dorsal thalamus-->prefrontal cortex, which is not activated in portacaval shunt rats. In these rats, DHPG activates an 'alternative' circuit: NAcc-->substantia nigra pars reticulata-->ventro-medial thalamus-->prefrontal cortex, which is not activated in control rats. The reasons by which liver failure leads to activation of this 'alternative' circuit remain unclear. The aim of this work was to assess whether hyperammonaemia could be responsible for the alterations found in chronic liver failure. We injected DHPG in NAcc of control or hyperammonaemic rats and analysed, by in vivo brain microdialysis, the neurochemical responses of the 'normal' and 'alternative' circuits. In hyperammonaemic rats DHPG injection in NAcc activates both the 'normal' and 'alternative' circuits. In hyperammonaemia, activation of the 'alternative' circuit and increased motor response following metabotropic glutamate receptors activation in NAcc seem due to an increase in extracellular glutamate which activates AMPA receptors.
Cauli
Omar
O
Laboratory of Neurobiology, Centro de Investigacion Príncipe Felipe, Valencia, Spain.
Mlili
Nisrin
N
Rodrigo
Regina
R
Felipo
Vicente
V
D000818:Animals; D004195:Disease Models, Animal; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D022124:Hyperammonemia / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D009043:Motor Activity / Q000187:drug effects*; D009434:Neural Pathways / Q000187:drug effects / Q000503:physiopathology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000503:physiopathology; D000644:Quaternary Ammonium Compounds; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects / Q000378:metabolism*; D012118:Resorcinols / Q000494:pharmacology*; D013378:Substantia Nigra / Q000187:drug effects / Q000503:physiopathology; D013788:Thalamus / Q000187:drug effects / Q000503:physiopathology
D018690:Excitatory Amino Acid Agonists; D000644:Quaternary Ammonium Compounds; D018094:Receptors, Metabotropic Glutamate; D012118:Resorcinols; C079215:3,5-dihydroxyphenylglycine; D005998:Glycine