Loss of dopaminergic nigrostriatal neurons accounts for the motivational and affective deficits in Parkinson’s disease

Abstract

Parkinson's disease (PD) involves the degeneration of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc) that is thought to cause the classical motor symptoms of this disease. However, motivational and affective impairments are also often observed in PD patients. These are usually attributed to a psychological reaction to the general motor impairment and to a loss of some of the neurons within the ventral tegmental area (VTA). We induced selective lesions of the VTA and SNc DA neurons that did not provoke motor deficits, and showed that bilateral dopamine loss within the SNc, but not within the VTA, induces motivational deficits and affective impairments that mimicked the symptoms of PD patients. Thus, motivational and affective deficits are a core impairment of PD, as they stem from the loss of the major group of neurons that degenerates in this disease (DA SNc neurons) and are independent of motor deficits.

Similar Roles of Substantia Nigra and Ventral Tegmental Dopamine Neurons in Reward and Aversion

“…Our data raise the possibility that loss of SNc DA neurons is sufficient to cause some of these affective deficits in Parkinson's patients. Consistent with this notion is that the recent report that selective 6-OHDA lesions of SNc DA neurons attenuate escape and avoidance from aversive stimuli (Drui et al, 2013). Moreover, in the VTA, optogenetic excitation and inhibition attenuate and facilitate depression-like symptoms, respectively (Tye et al, 2013).…”

Neural substrates underlying effort, time, and risk-based decision making in motivated behavior

“…Another study looked at the Substantia Niagra pars Compacta (SNc) on motivated behavior. This study induced partial lesions to the SNc which didn’t disrupt overall locomotor behavior resulted in decreased lever pressing in a PR for sucrose rewards, but these same effects were not observed with partial lesions of the VTA (Guillaume Drui et al, 2013). Additional evidence for the role of the Nigrostriatal DA system in motivated behavior comes from a recent study using a novel operant joystick based task.…”

A smaller amygdala is associated with anxiety in Parkinson’s disease: a combined FreeSurfer—VBM study

“…Lesioning of the substantia nigra pars compacta in rodents leads to anxiety-like behaviour that is reversed by dopamine agonist infusion,5 suggesting a causal role for dopamine dysfunction in the development of anxiety symptoms. Nevertheless, studies on whether dopamine replacement therapy can alleviate anxiety symptoms in patients with PD have been inconsistent6 7 and dysfunction of other neurotransmitters, such as serotonin and noradrenalin, are probably also involved in the development of anxiety in PD.…”