Behavioural impact of a double dopaminergic and serotonergic lesion in the non-human primate
2015
Brain
138(Pt 9):2632-47
Authors: 
Beaudoin M
Epinat J
Météreau E
Duperrier S
Neumane S
Ballanger B
Lavenne F
Liger F
Tourvielle C
Bonnefoi F
Costes N
Le Bars D
Broussolle E
Thobois S
Tremblay L
Sgambato-Faure V

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 symptomatolog, 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-Nmethamphetamine (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 neuropsychiatriclike 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.