Beschreibung:
<jats:p> <jats:bold>Abstract</jats:bold> : The role of the GABA<jats:sub>A</jats:sub> receptor
β<jats:sub>3</jats:sub> 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<jats:sub>3</jats:sub> 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<jats:sub>A</jats:sub> receptor
function in +/+ and +/‐ mice. In ‐/‐ mice, GABA<jats:sub>A</jats:sub> receptor function
was not decreased any further by repeated cocaine injections. Thus,
alterations in the β<jats:sub>3</jats:sub> 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.</jats:p>