| We
are interested in the development of the monoaminergic
neurotransmitter systems (i.e., dopamine,
DA; serotonin, 5-HT; and norepinephrine, NE)
and how these systems are influenced by early
exposure to drugs of abuse or compounds used
in the treatment of psychopathological disorders.
Much of our recent work has involved the use
of a rat model to determine the mechanisms
of cocaine action on the developing brain
and the neurochemical and behavioral consequences
of chronic prenatal cocaine exposure. Previous
studies had shown that cocaine binds to the
plasma membrane transporters for DA, NE, and
5-HT, thereby blocking the synaptic reuptake
of these transmitters and potentiating their
activity. We have determined the pharmacological
characteristics and distribution of these
transporters in fetal and adult brain using
several radioligands, including the cocaine
analog [125I]RTI-55 (which binds to both DA
and 5-HT transporters) as well as other drugs
that more selectively label individual transporter
subtypes.
Another possible target of developmental
cocaine action is the placenta, which expresses
both transporters and receptors for NE and
5-HT. We have investigated the normal distribution
of placental transporters using in vitro
autoradiography, and we have also shown
that maternal cocaine treatment up-regulates
the placental NE transporter and may down-regulate
the ß-adrenergic receptor system.
Current lab projects include the effects
of prenatal cocaine treatment on signal
transduction mechanisms and modulation of
DA-regulated neuropeptide gene expression
in the brain.
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