Abstract
Most physiologic processes in the brain and related diseases involve more than one neurotransmitter system. Thus, elucidation of the interaction between different neurotransmitter systems could allow for better therapeutic approaches to the treatments of related diseases. Dopaminergic (DAergic) and cholinergic neurotransmitter system regulate various brain functions that include cognition, movement, emotion, etc. This review focuses on the interaction between the brain DAergic and cholinergic systems with respect to the pathogenesis and treatment of schizophrenia and Parkinson’s disease (PD). We first discussed the selection of motor plans at the level of basal ganglia, the major DAergic and cholinergic pathways in the brain, and the receptor subtypes involved in the interaction between the two signaling systems. Next, the roles of each signaling system were discussed in the context of the negative symptoms of schizophrenia, with a focus on the α7 nicotinic cholinergic receptor and the dopamine D1 receptor in the prefrontal cortex. In addition, the roles of the nicotinic and dopamine receptors were discussed in the context of regulation of striatal cholinergic interneurons, which play crucial roles in the degeneration of nigrostriatal DAergic neurons and the development of L-DOPA-induced dyskinesia in PD patients. Finally, we discussed the general mechanisms of nicotine-induced protection of DAergic neurons.
Highlights
Owing to the roles of the brain dopaminergic (DAergic) system in addiction, interactions between the nicotinic cholinergic and DAergic systems have been extensively studied with respect to nicotine addiction [1,2]
Early nicotine exposure is accompanied by an increase in DA D3 receptor (D3R) expression [5], and D3R antagonists have been reported to be effective for the treatment of nicotine dependence [5,6]
In support of these observations, a recent study has shown the functional interaction between α4β2 nAChR and D3R [7]. In addition to their roles in nicotine addiction, the brain DAergic and nicotinic cholinergic systems are known to play important roles in the pathogenesis and management of the symptoms related to schizophrenia and Parkinson’s disease (PD)
Summary
Owing to the roles of the brain dopaminergic (DAergic) system in addiction, interactions between the nicotinic cholinergic and DAergic systems have been extensively studied with respect to nicotine addiction [1,2]. Early nicotine exposure is accompanied by an increase in DA D3 receptor (D3R) expression [5], and D3R antagonists have been reported to be effective for the treatment of nicotine dependence [5,6] In support of these observations, a recent study has shown the functional interaction between α4β2 nAChR and D3R [7]. In addition to their roles in nicotine addiction, the brain DAergic and nicotinic cholinergic systems are known to play important roles in the pathogenesis and management of the symptoms related to schizophrenia and Parkinson’s disease (PD).
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