Areas of Interest
Neuropharmacology; transmitter-receptor dynamics; neurobiology
of drug abuse; cellular and genetic adaptation to chronic drug
exposure. A major focus of our laboratory is the neurobiology of
emotion. We are particularly interested in the neural circuits
that underlie responses to stress. These brain pathways utilize
many signalling molecules including the transmitters
norepinephrine and dopamine and neuropeptides including the
endogenous opioids. These same pathways are also activated by
psychoactive drugs. We are exploring the connection between
early life stresses and later reactivity to stress and the
propensity to self-administer drugs of abuse. This process is
called stress sensitization and our studies show that the
sensitization caused by stress can endure for months or years.
This can be considered as a memory function of the emotional
circuits. Interestingly, sensitization can be blocked by
inhibitors of the NMDA-glutamate receptor. These studies are
carried out in rats and include techniques that allow monitoring
of neurochemical events from the brain of awake, freely moving
animals using in vivo microdialysis and assays for these
transmitters. A second focus involves the effects of ethanol on
brain neurons. Several preparations are used: one is the long
term effects of ethanol on the GABA-Benzodiazepine-chloride
channel where receptor changes can be assessed by binding
studies, receptor function assessed by ion flux assays and
receptor structure assessed by mRNA assays for receptor subunits
(with Dr. H. Yeh). Another preparation allows the study of
prenatal exposure to ethanol. This is a rodent model of Fetal
Alcohol Syndrome. In all of these studies, a major objective is
determining adaptation at the neuronal level and at the level of
gene expression to the chronic drug exposure.
Publications
Selected Publications
Shoemaker WJ, Vavrousek-Jakuba E, Arons CD, Kwok FC. The
acquisition and maintenance of voluntary ethanol drinking in the
rat: effects of dopaminergic lesions and naloxone. Behav Brain
Res. Dec 2;137(1-2):139-48, 2002.
Kehoe, P., Shoemaker, W.J., Arons, C., Triano, L. & Suresh,
G., Repeated isolation stress in the neonatal Rat: Relation to
Brain Dopamine Systems in the 10 Day Old Rat. Behavioral
Neuroscience 112: 1466-1474, 1998.
Kehoe, P., Shoemaker, W. J., Triano, L., Callahan, M., &
Rappolt, G., Adult rats stressed as neonates show exaggerated
behavioral responses to both pharmacological and environmental
challenges. Behavioral Neuroscience. 112: 116-125, 1998.
 View more publications, see
Pubmed listing. |
