title: Apomorphine-induced alterations in striatal and substantia nigra pars reticulata glutamate following unilateral loss of striatal dopamine.
abstract: We have reported time-dependent changes in extracellular glutamate within the striatum at 1 and 3 months following a unilateral lesion of the nigrostriatal pathway using the neurotoxin, 6-hydroxydopamine (6-OHDA) (Meshul, C.K., Emre, N., Nakamura, C.M., Allen, C., Donohue, M.K., Buckman, J.F., 1999. Time-dependent changes in striatal glutamate synapses following a 6-hydroxydopamine lesion. Neurosci. 88, 1-16.). The aim of the present study was to determine the effects of such a lesion on glutamate within the substantia nigra pars reticulata (SN-PR) and the effect of subchronic administration of the dopamine D-1/D-2 agonist, apomorphine, on extracellular glutamate within both the striatum and the SN-PR using in vivo microdialysis. One month after the lesion, there is an increase in extracellular glutamate within the striatum and apomorphine treatment leads to a further increase. Within the SN-PR, a loss of striatal dopamine leads to a decrease in extracellular glutamate, while apomorphine treatment leads to a further decrease in nigral glutamate. Three months after a 6-OHDA lesion, there is a decrease in extracellular striatal glutamate, with apomorphine administration leading to essentially no further change in glutamate. The loss of striatal dopamine increased extracellular glutamate within the SN-PR while apomorphine administration resulted in a decrease in extracellular glutamate back to the value observed in the control group. The data suggests that the increase in striatal glutamate 1 month following a 6-OHDA lesion alone or following subchronic apomorphine is consistent with the hypothesis that a decrease in glutamate within the SN-PR leads to activation of the thalamo-cortico-striatal pathway. The decrease in striatal glutamate 3 months after a nigrostriatal lesion is also consistent with the observed increase in extracellular glutamate within the SN-PR, thus leading to a decrease in output of the thalamo-cortico-striatal pathway.
authors.affiliation: Research Services, Neurocytology Lab, VA Medical Center, 3710 S.W. Veterans Hospital Road, Portland, OR 97239, USA.
authors.forename: Justin C
authors.initials: JC
authors.lastname: Touchon
authors.forename: Haley K
authors.initials: HK
authors.lastname: Holmer
authors.forename: Cynthia
authors.initials: C
authors.lastname: Moore
authors.forename: Brenda L
authors.initials: BL
authors.lastname: McKee
authors.forename: Julie
authors.initials: J
authors.lastname: Frederickson
authors.forename: Charles K
authors.initials: CK
authors.lastname: Meshul
mesh_terms: D000818:Animals; D001058:Apomorphine / Q000008:administration & dosage*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors
chemical_list: D018698:Glutamic Acid; D001058:Apomorphine; D004298:Dopamine