Serotonin 5-HT1A 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 sacr ificed and monoamine content was measured in different brain regions of the lesioned monkeys and of age-matched controls. 5-HT1A serotonin receptor de nsity was measured in coronal sections labeled with [H-3]8-OH-DPAT. As expe cted, dopamine was virtually nonexistent in the caudate nucleus and putamen of MPTP-treated monkeys. Serotonin levels were significantly reduced in di fferent brain regions, particularly in the raphe nuclei. 5-HT1A receptor de nsity of control animals was high in the hippocampus, notably in the CA1 fi eld and also in the raphe nuclei, and much lower in the striatum, where 5-H T1A receptors showed a patchy distribution which corresponded to striosomes with poor calbindin immunostaining. 5-HT1A receptor density was reduced in hippocampal fields and in the raphe nuclei of parkinsonian monkeys. Conver sely, in the severely lesioned striatal nuclei 5-HT1A receptor density was increased at caudal levels of the striatum, particularly in the putamen. Th e 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 ma y represent a compensatory event for the serotonergic dysfunction and assoc iated mental disorders in neurodegenerative diseases such as Parkinson dise ase. Synapse 39: 288-296, 2001. (C) 2001 Wiley-Liss, Inc.