Expertise:
Behavioral pharmacology and
neuroscience in rodents; biochemistry (in vivo microdialysis
and HPLC); receptor binding and protein assay
My research is generally concerned with understanding how
the neurotransmitters of the basal ganglia contribute to
the generation of appetitive behaviors. I am particularly
interested in understanding how the ascending mesencephalic
dopamine systems impact the pursuit and self-administration
of psychotropic drugs like amphetamine, cocaine and nicotine.
These groups of neurons, while relatively small, project
to a large number of forebrain sites and are known to profoundly
influence motor and affective behaviors. We are interested
in determining how these systems interact with others to
produce such effects and how these neurotransmitter interactions
may be changed when an organism is exposed repeatedly to
pharmacological and environmental stimuli. We and others
have shown that exposing rats repeatedly to psychotropic
drugs or environmental stressors leads to the induction and
eventual expression of sensitization (reverse tolerance)
in mesolimbic dopamine neurotransmission.
Our research is aimed, first, at determining how this sensitization
is produced and, second, at understanding how such changes
may influence the expression of various behaviors in the
rat. In the first case, we are using a variety of behavioral,
intravenous and intracranial drug delivery, biochemical,
neuropharmacological, receptor binding, subcellular fractionation
and gene delivery techniques to determine which aspects of
dopamine neurotransmission become enhanced (transmitter release,
receptor regulation and function) and to assess the contribution
of other neurotransmitter projections and receptor fields
(excitatory amino acids, ACh, GABA). In the second, we are
currently investigating the relation between the expression
of sensitization in the mesocorticolimbic dopamine and glutamate
systems and an organism's predisposition to express substance
abuse profiles. We are assessing the extent to which various
manipulations, known to sensitize dopamine and glutamate
neuron reactivity, promote psychotropic drug seeking and
self-administration in rats.
Specific research projects:
-- Using viral mediated gene transfer to study the effect
of over-expressing different forms of CaMKII in different
brain regions on amphetamine-induced behaviors and changes
in neurotransmitter overflow
-- Using pharmacological agents to study the effect of
inhibiting CaMKII in nucleus accumbens subregions on enhanced
amphetamine self-administration
-- Using total protein assays and subcellular fractionation
to assess the effect of exposure to sensitizing regimens
of amphetamine injections on AMPA receptor subunit levels
and trafficking in nucleus accumbens subregions
-- Identify and characterize the state of nAChRs in different
brain regions that contribute to locomotor sensitization
by nicotine
-- Assessing how conditioned inhibitors modulate the expression
of behavioral sensitization
Laboratory personnel:
Anitra Guillory, Ph.D. Graduate Student
amg2001@uchicago.edu
Bryan Singer, Undergraduate Student
bfsinger@uchicago.edu
Derek Tucker, M.D./Ph.D. Student
dctucker@uchicago.edu
Etha Williams, Undergraduate Student
ejwillia@uchicago.edu
Jessica Loweth, Ph.D. Student
jloweth@uchicago.edu
John Scott-Railton, Junior Technician
jsrailto@uchicago.edu
Karolina Kalita, Undergraduate Student
kalita@uchicago.edu
Kathy Nosek, Undergraduate Student
kmn@uchicago.edu
Lauren Singletary, Prep Scholar
lsingletary@peds.bsd.uchicago.edu
Lorinda Baker, Senior Technician
lbaker@yoda.bsd.uchicago.edu
Tarra Barot, Postdoctoral Fellow
tbarot@yoda.bsd.uchicago.edu |
