Defining the neurobiological basis of central adaptation chronic administration ethanol and psychotropic drugs.
Modeling of symptoms of central disorders
Research Synopsis:
The primary focus of our laboratory is to understand adaptive change in brain that accompanies
lesioning of specific neural systems, stress, prolonged alcohol exposure and extended psychotropic
drug treatment. One area of focus is defining the underlying basis of the accumulating adaptation
that accompanies repeated exposures and withdrawals—an adaptation responsible for sensitization
of withdrawal-induced anxiety-like behavior and voluntary intake of alcohol. A second area of interest
is the role stress plays in maintaining alcohol abuse by sensitization of anxiety-like behavior after
previous exposure to chronic alcohol. These initial two areas of research provide a means to understanding
the process of alcohol abuse. Behavioral, pharmacological, dialysis, drug microinjection, biochemical,
gene knockout, and electrophysiological techniques are utilized for this research. A third area of interest
is the basis of persistent change in transcription factors that accompanies repeated administration of a
D1 -dopamine receptor agonist to rats with dopamine-containing neurons destroyed during development.
This treatment models the dopamine deficiency observed in Lesch-Nyhan disease. In this model, the
laboratory is also interested in defining the basis of the NMDA hypofunction observed, which emulates
the NMDA hypofunction characteristic of schizophrenia. These latter areas of research involve biochemical
and neuroanatomical assessments coupled to microarray results. The final research area involves an effort
to understand the cellular action of ethanol to alter the function of some but not all neurons in brain.
For this phase, brain slices and isolated neurons are utilized to provide electrophysiological analysis.
Recent Publications:
Breese, G.R., Criswell, H.E., Carta, M., Dodson, P., Hanchar, H.J., Khisti, R.T., Mameli, M., Ming, Z.,
Morrow, A.L., Olsen, R.W., Otis, T.S., Parsons, L.H., Penland, S.N., Roberto, M., Siggins, G.R.,
Valenzuela, C.F., and Wllner, M. (2006) Basis of the GABAmimetic profile of ethanol. Alcoholism: Clin Exp Res [in press].
Overstreet, D.H., Knapp, D.J., Angel, R.A., and Breese, G.R. (2006) Reduction in
repeated ethanol withdrawal-induced anxiety-like behavior by
site-selective injections of 5-HT_1A and 5-HT_2c ligands. Psychopharmacology [in press].
Breese, G.R., Overstreet, D.H., Knapp, D.J., Navarro, M. (2005) Prior multiple ethanol withdrawals enhance stress-induced anxiety-like behavior during
extended abstinence: Inhibition by CRF-1 and benzodiazepine receptor antagonists and by a 5-HT_1A -receptor agonist. Neuropsychopharmacology
30: 1662-1669. Abstract
Hayes, D.H.. Knapp, D.J., Breese, G.R., Thiele T.E. (2005) Comparison of basal NPY and CRF levels between the high ethanol drinking C57BL/6J and low
ethanol drinking DBA/2J inbred mouse strains. Alcohol Clin Exp Res 29: 721-729. Abstract
Breese, G.R., Chu, K., Dayas, C.V., Funk, D., Knapp, D.J.,
Koob, G.F., Le D.A., O’Dell, L.E., Overstreet, D.H., Roberts, A.J., Sinha, R., Valdez, G.R., and Weiss, F. (2005) Stress enhancement of craving during sobriety: a risk of relapse.
Alcohol Clin Exp Res29: 185-195. Abstract
Breese, G.R., Overstreet, D.H., and Knapp, D.J. (2005) Conceptual framework for the etiology of alcoholism: a “kindling”/stress hypothesis.
Psychopharmacology 178: 367-380. Abstract
