Serotonin 5-HT(1A) receptor expression is selectively enhanced in the striosomal compartment of chronic parkinsonian monkeys.
Cynomolgus monkeys (Macaca fascicularis) were chronically treated with the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) until stable parkinsonism was reached. Two months later, monkeys were sacrificed and monoamine content was measured in different brain regions of the lesioned monkeys and of age-matched controls. 5-HT(1A) serotonin receptor density was measured in coronal sections labeled with [(3)H]8-OH-DPAT. As expected, dopamine was virtually nonexistent in the caudate nucleus and putamen of MPTP-treated monkeys. Serotonin levels were significantly reduced in different brain regions, particularly in the raphe nuclei. 5-HT(1A) receptor density of control animals was high in the hippocampus, notably in the CA1 field and also in the raphe nuclei, and much lower in the striatum, where 5-HT(1A) receptors showed a patchy distribution which corresponded to striosomes with poor calbindin immunostaining. 5-HT(1A) receptor density was reduced in hippocampal fields and in the raphe nuclei of parkinsonian monkeys. Conversely, in the severely lesioned striatal nuclei 5-HT(1A) receptor density was increased at caudal levels of the striatum, particularly in the putamen. The results tend to support the possibility of an increased synthesis of 5-HT(1A) receptors in brain regions with higher neuronal cell death. Upregulation of this 5-HT receptor subtype in the limbic compartment of the striatum may represent a compensatory event for the serotonergic dysfunction and associated mental disorders in neurodegenerative diseases such as Parkinson disease.
Frechilla
D
D
Department of Pharmacology, University of Navarra Medical School, 31080-Pamplona, Spain.
Cobreros
A
A
Saldise
L
L
Moratalla
R
R
Insausti
R
R
Luquin
M
M
Del Río
J
J
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000378:metabolism; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents; D015870:Gene Expression; D008252:Macaca fascicularis; D008297:Male; D017072:Neostriatum / Q000378:metabolism*; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000378:metabolism*; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin / Q000378:metabolism
D015259:Dopamine Agents; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine