3-amino-4-(2-dimethylaminomethylphenylsulfanyl)benzonitrile and Mental-Disorders

Serotonergic (5-HT) neurons degenerate in Parkinson's disease. To determine the role of this 5-HT injury-besides the dopaminergic one in the parkinsonian symptomatology-we developed a new monkey model exhibiting a double dopaminergic/serotonergic lesion by sequentially using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 3,4-methylenedioxy-N-methamphetamine (MDMA, better known as ecstasy). By positron emission tomography imaging and immunohistochemistry, we demonstrated that MDMA injured 5-HT nerve terminals in the brain of MPTP monkeys. Unexpectedly, this injury had no impact on tremor or on bradykinesia, but altered rigidity. It abolished the l-DOPA-induced dyskinesia and neuropsychiatric-like behaviours, without altering the anti-parkinsonian response. These data demonstrate that 5-HT fibres play a critical role in the expression of both motor and non-motor symptoms in Parkinson's disease, and highlight that an imbalance between the 5-HT and dopaminergic innervating systems is involved in specific basal ganglia territories for different symptoms.

Topics: Aniline Compounds; Animals; Antiparkinson Agents; Brain; Brain Mapping; Chlorocebus aethiops; Disease Models, Animal; Dopamine; Dopamine Agents; Female; Levodopa; Macaca fascicularis; Male; Mental Disorders; MPTP Poisoning; N-Methyl-3,4-methylenedioxyamphetamine; Nortropanes; Radionuclide Imaging; Serotonin; Serotonin Agents; Sulfides