Catecholamine/Serotonin interactions: systems thinking for brain function and disease.
A New Era of Catecholamines in the Laboratory and Clinic. 2013-01-01; : 167-197
DOI: 10.1016/B978-0-12-411512-5.00009-9
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This chapter brings together the work of several leading laboratories, each an
outstanding example of integrative approaches to complex diseases of the central
nervous system. Cognitive dysfunction and negative symptoms associated with
schizophrenia are believed to result from hypofunction of the mesocortical
dopaminergic projections to prefrontal cortex (PFC). Noradrenergic targets for
the augmentation of dopaminergic function in PFC show promise to improve
cognitive deficits as well as negative symptoms. Serotonergic targets for the
modulation of mesocortical dopaminergic neurotransmission include 5-HT2A and
5-HT1A receptors. The hallmark of Parkinson’s disease is the destruction of
nigrostriatal dopaminergic neurons. l-DOPA, a metabolic precursor of dopamine, is
the standard of treatment. However, the ectopic release of dopamine (DA) from
serotonin neurons and the clearance of extracellular DA by the norepinephrine
transporter in areas enriched with noradrenergic terminals contribute to
extracellular DA produced by l-DOPA and offer opportunities to improve l-DOPA
therapy. The high-affinity transporters for monoamines are the primary targets
for antidepressant drugs. However, many patients experience suboptimal
therapeutic benefit or fail to respond to treatment. Organic cation transporters
and plasma membrane monoamine transporter serve an important function in
regulating monoamine neurotransmission and hold potential utility as targets for
the development of therapeutic drugs. Improved therapeutic approaches will arise
from not only understanding how monoamines influence one another within the
central nervous system as an integrated whole but also addressing the
pathophysiology of specific core symptoms or distinct syndromal dimensions
(cognitive impairment, motor slowing, and negative affect) regardless of disease
classification, for example, psychotic, affective, and neurodegenerative.
© 2013 Elsevier Inc. All rights reserved.