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Journal of Neuroscience, Vol 9, 2051-2065, Copyright © 1989 by Society for Neuroscience
Concomitant characterization of behavioral and striatal neurotransmitter response to amphetamine using in vivo microdialysis
R Kuczenski and D Segal
Department of Psychiatry, University of California, San Diego, La Jolla 92093.
The temporal and dose-related behavioral and striatal monoamine response to
amphetamine (AMPH) was examined using in vivo microdialysis in freely
moving rats. Extracellular dopamine (DA), serotonin (5-HT), and their
metabolites were monitored concomitant with detailed characterization of
the locomotor and stereotypy profiles. Consistent with previous results,
AMPH (0.5-5.0 mg/kg) induced a rapid dose- dependent increase in DA
concentration and decrease in the concentrations of the DA metabolites,
DOPAC and HVA. DA and its metabolites exhibited contrasting temporal and
dose-related patterns, suggesting that the decline in DA metabolites is
functionally dissociated from the AMPH-enhanced DA release. In addition,
AMPH at doses of 2.0 mg/kg and greater significantly increased
extracellular concentrations of 5-HT, which, in contrast to the changes in
dopamine, persisted for only 20-40 min. Comparisons of concentrations of DA
and 5- HT for individual animals revealed significant correlations both
during baseline and drug response, suggesting a possible functional
interdependence between dopaminergic and serotonergic activity in striatum.
Dose-response comparisons revealed a significant relationship between
AMPH-induced increases in behavioral perseveration and the magnitude and
duration of the DA release. However, the temporal patterns of the
neurotransmitter response and individual components of stereotypy were not
parallel, suggesting that the presence of stereotypies is not associated
simply with quantitative differences in striatal DA release. By contrast,
some features of the behavioral response were significantly correlated with
AMPH-induced changes in striatal 5-HT concentrations. Our results suggest
that the behavioral response to AMPH may be influenced by the interaction
between levels of DA and 5-HT release, as well as by the state of their
respective receptors.
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