M sub(4) muscarinic receptors regulate the dynamics of cholinergic and dopaminergic neurotransmission: relevance to the pathophysiology and treatment of related CNS pathologies

Dopaminergic dysfunction is an important pathogenetic factor for brain pathologies such as Parkinson's disease, ADHD, schizophrenia, and addiction as well as for metabolic disorders and anorexia. Dopaminergic neurons projecting from the midbrain to forebrain regions, such as the nucleus accumbens and the prefrontal cortex, regulate motor and cognitive functions and coordinate the patterned response of the organism to sensory, affective, and rewarding stimuli. The aim of this study was to determine the role of the inhibitory metabotropic cholinergic receptors (M sub(2) and M sub(4) receptors) in regulating dopaminergic and cholinergic neurotransmission in the whole animal, and thus to examine the potential of these receptors as therapeutic molecular targets for diseases in which the dynamic balance of the two neurotransmitter systems is purportedly disrupted.