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Research Overview

By the early 1980s it had become evident that many neurotransmitter receptors that are targets for many drugs and environmental chemicals appear very early in brain development, often before the neurons containing them receive presynaptic input. The presence of these receptors might render developing cells vulnerable to changes in their chemical environment, permitting endogenous and exogenous chemicals (such as drugs) to influence development, perhaps altering the organization of the nervous sytem. My research program is directed to exploring this idea.

In my first work to test this hypothesis, I examined how manipulation of the GABA_A receptor influences the early development of the nervous system. GABA is the major inhibitory transmitter in the adult mammalian brain and is diffusely distributed. However, during early brain development, depolarizes neurons, and trophic effects have been attributed to this substance. Interference with GABA systems during development might therefore be expected to have far-reaching effects. Using a variety of neurochemical, neuroanatomical, physiological and behavioral methods to evaluate the effects of early manipulation of the GABA_A receptor on the nervous system and on behavior, we have found that drugs such as diazepam (Valium), which enhances the action of GABA at the receptor, do indeed have profound effects on a range of adaptive responses of a kind that are often not expressed until adolescence (a stage at which many clinical behavioral disorders appear), and long after the drug has been cleared from the body. These studies have led to others that focus on related questions. For example, how do particular stressor-responsive systems change during adolescent development and what is the underlying trigger for the change; do gonadal steroids interact with responses mediated via the GABA_A receptor during early development and how does concurrent diazepam exposure alter this influence? We are currently evaluating the effect of early manipulation of the GABA_A receptor on the expression of specific neurotrophic factors.

Research Interests

• neuropharmacology
• development
• hormones
• behavior
• GABA