Imaging Dopamine and Serotonin Systems on MPTP Monkeys: A Longitudinal PET Investigation of Compensatory Mechanisms.

Unlabelled: It is now widely accepted that compensatory mechanisms are involved during the early phase of Parkinson's disease (PD) to delay the expression of motor symptoms. However, the neurochemical mechanisms underlying this presymptomatic period are still unclear. Here, we measured in vivo longitudinal changes of both the dopaminergic and serotonergic systems in seven asymptomatic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-intoxicated monkeys (when motor symptoms are less apparent) using PET.

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

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.

Cortico-basal ganglia circuits involved in different motivation disorders in non-human primates.

The ventral striatum (VS) is of particular interest in the study of neuropsychiatric disorders. In this study, performed on non-human primates, we associated local perturbation with monosynaptic axonal tracer injection into medial, central and lateral VS to characterize anatomo-functional circuits underlying the respective expression of sexual manifestations, stereotyped behaviors and hypoactive state associated with loss of food motivation. For the three behavioral effects, we demonstrated the existence of three distinct cortico-basal ganglia (BG) circuits that were topographically organized and overlapping at some cortical (orbitofrontal cortex, anterior cingulate cortex) and subcortical (caudal levels of BG) levels, suggesting interactions between motivation domains.

Towards a primate model of Gilles de la Tourette syndrome: anatomo-behavioural correlation of disorders induced by striatal dysfunction.

Introduction: Gilles de la Tourette syndrome (GTS) is characterized by abnormal movements (tics) often associated with behavioural disorders. Neuropathological data from GTS patients have suggested that aberrant activation of distinct striatal functional territories could produce a large spectrum of GTS symptoms. In a monkey model, injections of GABA-antagonist into the striatum enabled us to produce tic-like movements, hyperactivity and stereotyped behaviours.

Effects of dopamine and serotonin antagonist injections into the striatopallidal complex of asymptomatic MPTP-treated monkeys.

The cardinal symptoms of Parkinson's disease (PD), akinesia, rigidity and tremor, are only observed when the striatal level of dopamine (DA) is decreased by 60-80%. It is likely that compensatory mechanisms during the early phase of DA depletion delay the appearance of motor symptoms. In a previous study, we proposed a new PD monkey model with progressive MPTP intoxication.

Discontinuous long-train stimulation in the anterior striatum in monkeys induces abnormal behavioral states.

The striatum has been identified as a new target for therapeutic deep brain stimulation in the treatment of neurological and psychiatric disorders. The nonhuman primate model offers opportunities for detailed mapping of the behavioral effects of stimulation within the striatum. We recently showed that dysfunction in the dorsal and ventral striatum was able to produce a specific pattern of abnormal movements and behavioral states.