MAILMAN RESEARCH CENTER
Neuropharmacology Laboratory
Mailman Research Center |
Since Since 1969 the Neuropharmacology Laboratory has conducted
neurochemical, physiological, and histochemical studies of the effects of known
and novel drugs on central monoaminergic neurotransmission systems, with special
interest in the pharmacology of dopamine receptors and transporters in mammalian
brain. Laboratory collaborations include development of novel ligands for dopamine
receptors and transporters with medicinal and radiochemists. Collaborative clinical
studies on the treatment of major mental illnesses involve members of McLean's
Bipolar & Psychotic Disorders and Psychopharmacology Programs, also directed
by Professor Baldessarini, as well as with colleagues in other centers.
Current laboratory projects include quantitative autoradiographic analysis of
long-term effects of typical, atypical, and novel antipsychotic drugs on the
level and distribution of dopaminergic, serotonergic, glutamatergic and other
receptors in rat forebrain, following indications that cortical D2 and striatal
D4 receptors are common sites of action of antipsychotics. Other projects include
developing novel ligands, radioligands, and alkylating agents selective for
D1, D3, and D4 dopamine receptors, dopamine and serotonin transporters, and
serotonin receptors, as well as comparisons of the pharmacology of dopamine
transporters defined with known and novel radioligands. Lesioning studies seek
to refine the histolocation of dopamine and glutamate receptor subtypes, including
recent identification of D4 heteroceptors with NMDA autoreceptors on glutamatergic
corticostriatal projections, and NMDA and kainate autoreceptors on hippocampostriatal
terminals.
Quantitative behavioral analyses have mapped behavioral responses throughout
rat nucleus accumbens, and are used to evaluate actions of known and novel dopamine
agonists and antagonists in normal and selectively lesioned and intact developing
and mature rats. The laboratory has a long-standing interest in adaptive responses
to long-term treatment with dopamine agonists and antagonists, and was first
to quantitatively demonstrate supersensitivity of dopamine receptor functions
and to suggest its role in neuropsychiatric disorders including tardive dyskinesia.
Collaborative clinical projects include quantitative assessment of the effects
of discontinuing psychotropic drugs that include sharp, time-limited, increases
in morbidity and mortality. Such effects complicate clinical management of patients
and the ethical design and sound interpretation of studies involving drug discontinuation
or drug-placebo comparisons. Other studies include analyses of the impact of
shortening hospital length-of-stay on outcome in psychotic disorders, the course
of first-episode bipolar and psychotic disorder patients, as well as defining
factors that predict clinical response, outcome, and suicide risk in manic-depressive
and psychotic patients.
Personnel
- Ross J. Baldessarini, MD, Director, Neuropharmacology Laboratory (e-mail)
- Frank I. Tarazi, Ph.D., Associate Neuropharmacologist (e-mail)
- Leonardo Tondo, M.D., Research Associate (e-mail)
- Kehong Zhang, M.D., Ph.D., Assistant Neuropharmacologist (e-mail)
- Alexander Campbell, M.Phil., Research Associate (e-mail)
- Nora S. Kula, M.S., Associate Investigator (e-mail)