Behavioural impact of a double dopaminergic and serotonergic lesion in the non-human primate

作者：Beaudoin Gobert Maude; Epinat Justine; Metereau Elise; Duperrier Sandra; Neumane Sara; Ballanger Benedicte; Lavenne Franck; Liger Francois; Tourvielle Christian; Bonnefoi Frederic; Costes Nicolas; Le Bars Didier; Broussolle Emmanuel; Thobois Stephane; Tremblay Leon; Sgambato Faure Veronique^*

来源：Brain, 2015, 138(9): 2632-2647.

DOI：10.1093/brain/awv183

• Parkinson's disease
• dyskinesia
• neuropsychiatric symptoms
• serotonin
• monkey

To determine the role of serotonergic degeneration in Parkinson's disease, Beaudoin-Gobert et al. use sequential MPTP and MDMA to produce a monkey model with a double dopaminergic/serotonergic lesion. Damage to serotonin fibres has no effect on tremor or bradykinesia, but alters rigidity and abolishes L-DOPA-induced dyskinesias and neuropsychiatric symptoms.To determine the role of serotonergic degeneration in Parkinson's disease, Beaudoin-Gobert et al. use sequential MPTP and MDMA to produce a monkey model with a double dopaminergic/serotonergic lesion. Damage to serotonin fibres has no effect on tremor or bradykinesia, but alters rigidity and abolishes L-DOPA-induced dyskinesias and neuropsychiatric symptoms.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.

• 出版日期2015-9-1