Role of catecholamine signaling in brain and nervous system functions: new insights from mouse molecular genetic study.

Catecholamines, including dopamine and norepinephrine, are the principal neurotransmitters that mediate a variety of the central nervous system functions, such as motor control, cognition, emotion, memory processing, and endocrine modulation. Dysfunctions in catecholamine neurotransmission are implicated in some neurologic and neuropsychiatric disorders. Recent mouse molecular genetic approaches provide genetic evidence for an important role of catecholamines in brain functions. In this paper, I describe the phenotype of mutant mice with impairments in dopamine or norepinephrine biosynthesis. Mice defective in dopamine biosynthesis exhibit severe motor dysfunctions characterized by a reduction in spontaneous locomotion and cataleptic behavior, and defects in drug-induced hyperactivity at the juvenile stage. They also exhibit defects in the acquisition of conditioned learning dependent on tone stimulus. These results indicate that dopamine is essential for motor control and emotional learning during postnatal development, possibly through nigrostriatal and mesolimbic neuronal pathways. On the other hand, mice carrying the mutation in the gene encoding tyrosine hydroxylase (the rate-limiting enzyme of catecholamine biosynthesis) display a reduction in norepinephrine biosynthesis. This leads to deficits in latent learning and long-term memory formation of different conditioned learning paradigms. The results indicate that norepinephrine is essential for the consolidation process of long-term memory, suggesting that norepinephrine may control the neuronal activity in the cerebral cortex or amygdala to maintain the memory process of conditioned learning.