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Neuropharmacology of drugs of abuse, using electrophysiological
and behavioral endpoints; application to models of schizophrenia.
Research Activities
Ongoing research projects are seeking to identify the sites and
mechanisms of action by which drugs of abuse (marijuana, PCP,
inhalants, nicotine) affect the activity of midbrain dopamine
neurons in the rat. Paradoxically compounds like PCP and marijuana,
which are self-administered for their rewarding effects, can also
elicit behavioral alterations resembling the symptomatology seen
in schizophrenia. However, the mechanisms by which the different
drugs of abuse may be psychotomimetic, as well as rewarding, via
effects on dopamine activity is poorly understood. Moreover, the
neurophysiological underpinnings controlling dopamine neuronal
excitability are also not clearly delineated. Our approach to
the problem of drug-dopaminergic interactions is to use a variety
of neuropharmacologic techniques carried out on the rat and mouse,
with emphasis on electrophysiology. Toward this aim extracellular
recordings are performed in the anesthetized animal under various
drug treatment designs. Extra- and Intracellular recordings from
dopamine neurons in brain slice preparations have also been used
to examine the interaction of drugs and specific neurotransmitters
on activity and ion conductance mechanisms in these neurons. Small
quantities of drugs can also be applied directly onto single nerve
cells for mechanistic studies of drug action. In addition, the
use of techniques to eliminate or deplete essential transmitter
substances in whole animals are often combined with behavioral
measures designed to assess the potential role of various anatomical/transmitter
inputs onto these dopamine neurons. Also molecular techniques,
done in collaboration with other investigators, seek to identify
the site of action for nicotine-induced stimulation of midbrain
dopamine neurons.
Publications (Query PubMed for this investigator)
Wu, X and French, E.D.: Effects of anandamide on ventral tegmental
dopamine neuronal activity: comparison to delta-9 THC and WIN
55, 212-2, submitted, 2002.
Riegel, A. and French, E.D.: Abused inhalants and central reward
pathways: Electrophysiological and behavioral studies in the rat.
Annals N.Y. Academy of Sciences 965: 1-11, 2002,
Riegel, A. and French, E.D.: Behavioral tolerance from repeated
toluene exposure is paralleled by reduced VTA dopamine spontaneous
neuronal activity and responsiveness to toluene, and increased
sensitivity of non-DA neurons to NMDA. Society for Neuroscience,
Abstract, 2001.
French, E.D. and Riegel,A.: The excitatory effects of the abused
inhalant toluene in rat VTA neurons in vitro appears not to be
mediated by NMDA receptor activation. Society for Neuroscience,
Abstract, 2001.
Yin, R. and French, E.D.: A comparison of the effects of nicotine
on dopamine and non-dopamine neurons in the rat ventral tegmental
area: an in vitro electrophysiological study. Brain Research Bulletin
51: 507-514, 2000.
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