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Increased Acute Cocaine Sensitivity and Decreased Cocaine Sensitization in GABA A Receptor β 3 Subunit knockout Mice
Author(s) -
Resnick Adam,
Homanics Gregg E.,
Jung Bruce J.,
Peris Joanna
Publication year - 1999
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1999.0731539.x
Subject(s) - sensitization , neurochemical , striatum , knockout mouse , gabaa receptor , amphetamine , endocrinology , medicine , receptor , stimulation , pharmacology , agonist , dopamine , chemistry , psychology , neuroscience
: The role of the GABA A receptor β 3 subunit in determining acute cocaine sensitivity and behavioral sensitization to repeated cocaine was measured in mice missing both (‐/‐), one (+/‐), or neither (+/+) allele of the β 3 gene. Locomotor stimulation induced by one cocaine injection (20 mg/kg, i.p.) was found to be greater in ‐/‐ mice compared with +/+ mice, whereas cocaine‐induced behaviors were intermediate in +/‐ mice. Amphetamine did not cause greater locomotor responses in ‐/‐ mice, suggesting that the increased sensitivity of ‐/‐ mice to cocaine does not generalize to other psychomotor stimulants. GABA‐stimulated chloride uptake was 51% lower in striatum of ‐/‐ mice compared with +/+ mice, but only 27% lower in cortex. After 14 daily cocaine injections, the behavioral response to cocaine was increased in +/+ and +/‐ mice, but was not increased further in ‐/‐ mice. Additionally, repeated cocaine exposure decreased striatal GABA A receptor function in +/+ and +/‐ mice. In ‐/‐ mice, GABA A receptor function was not decreased any further by repeated cocaine injections. Thus, alterations in the β 3 subunit may be responsible for determining the behavioral responses induced by acute and repeated cocaine treatment, as well as mediating the neurochemical adaptation that occurs during sensitization to repeated cocaine.