Biomedical Engineering Reference
In-Depth Information
after withdrawal from repeated cocaine treatment. However, alterations are
observed at later withdrawal times, and they differ from those produced by
amphetamine. Churchill et al.
(14)
used Western blotting to determine protein
levels of glutamate receptor subunits 24 h or 3 wk after discontinuing daily
cocaine or saline injections (
see
Subheading 2.2.
for more details). After 24 h,
there were no changes in GluR1 or NMDAR1 levels in the NAc, consistent
with the fi ndings of Fitzgerald et al.
(12)
. However, after 3 wk, sensitized
rats (but not cocaine-treated rats that failed to sensitize) showed a signifi cant
increase in GluR1 levels in the NAc compared to saline-treated rats. When
saline-treated rats were compared to all cocaine rats (sensitized + nonsensi-
tized), there was a trend toward increased NMDAR1 in the NAc after repeated
cocaine, but this was actually more pronounced in nonsensitized rats. GluR2/3
was not changed in the NAc at either withdrawal time. Dorsal striatum was
analyzed only after 3 wk of withdrawal; there were no changes in GluR1,
GluR2/3, or NR1. Likewise, these subunits were unchanged in prefrontal
cortex or VTA after 3 wk of withdrawal, although increases in GluR1 and
NR1 were found in VTA of sensitized rats 24 h after discontinuing cocaine
(
see
Subheading 2.2.
).
Interestingly, the changes in protein levels found by Churchill et al.
(14)
were not paralleled by changes at the mRNA level. Ghasemzadeh et al.
(22)
used
in situ
hybridization histochemistry and RT-PCR to quantify glutamate
receptor subunit mRNA levels 3 wk after discontinuing the same regimen of
cocaine or saline injections used by Churchill et al.
(14)
. Twenty-four hours
before decapitation, half the rats in each group were challenged with saline and
half with cocaine. In NAc, acute cocaine decreased mRNA levels for GluR3,
GluR4, and NR1, while repeated cocaine also decreased GluR3 mRNA and
increased mGluR5 mRNA. The only signifi cant effect in dorsolateral striatum
was decreased NR1 mRNA after acute cocaine. The VTA and PFC were also
evaluated (see
Subheadings 2.2.
and
4.2.
). Because of the complexity of
the design, the reader should consult the article for an in-depth discussion
of interactions between chronic cocaine treatment and acute challenge, and
interesting trends that were apparent in some groups.
Scheggi et al.
(44)
used Western blotting to measure glutamate receptor
subunits after administering 40 mg/kg of cocaine every other day over 14 d,
testing for sensitization after 10 d of withdrawal, and killing the rats 1 wk after
the test for sensitization. In NAc, signifi cant increases in GluR1, NR1, and
NR2B (but not GluR2 or NR2A) were found in sensitized rats. The changes in
GluR1 and NR1 are in agreement with those reported by Churchill et al.
(14)
. In
hippocampus, only the NR2B subunit was signifi cantly elevated although there
was a trend toward increased NR1 (26% increase). In the PFC, small increases
(~20%) were observed for NR1 and NR2B, but these were not signifi cant, and
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