Roles of the Functional Interaction between Brain Cholinergic and Dopaminergic Systems in the Pathogenesis and Treatment of Schizophrenia and Parkinson's Disease

Int J Mol Sci. 2021 Apr 21;22(9):4299. doi: 10.3390/ijms22094299.


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.

Keywords: L-DOPA; Parkinson’s disease; dopamine; nicotine; receptor; schizophrenia.

Publication types

  • Review

MeSH terms

  • Animals
  • Brain / metabolism
  • Brain / pathology*
  • Cholinergic Agents / metabolism*
  • Dopamine / metabolism*
  • Dopaminergic Neurons / metabolism*
  • Humans
  • Parkinson Disease / metabolism
  • Parkinson Disease / pathology*
  • Parkinson Disease / therapy
  • Schizophrenia / metabolism
  • Schizophrenia / pathology*
  • Schizophrenia / therapy


  • Cholinergic Agents
  • Dopamine