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Figure 15.7
PHA-543613 evokes a7 nAChR-mediated currents from rat hippo-
campal neurons. Reproduced with permission of the American Chemical
Society from J. Med. Chem., 2006, 49, 4425.
100
80
#
##
60
40
*
20
0
Control
AMP + PHA-543613
(0.3 mg/kg)
AMP + PHA-543613
(1.0 mg/kg)
(mg kg
-1
, SC)
AMP
A
B
Figure 15.8
(A) Effect of PHA-543613 (0.3 and 1mg kg
1
sc) on the auditory gating
deficit in amphetamine-treated rats: * P
o
0.001 vs. control; # P
o
0.02 vs.
d-amphetamine (AMP); ## P
o
0.005 vs. AMP. (B) PHA-543613
improves performance in the rat novel object recognition task: * P
o
0.05.
Adapted with permission of the American Chemical Society from
J. Med. Chem., 2006, 49, 4425.
nAChR agonist PHA-543613 (0.3 or 1mg kg
1
iv) significantly reverses the d-
amphetamine-induced gating deficit (Figure 15.8A). In contrast, application of
vehicle in control rats did not normalize the d-amphetamine-induced gating
deficit.
The potential for PHA-543613 to influence learning and memory was eval-
uated using the rat novel object recognition (NOR) task model.
39
This test is
based on the ethological observation that rats spend more time exploring
objects they have never seen (novel objects) than objects that are familiar.
40
PHA-543613 was administered at 0.3mg kg
1
or 1mg kg
1
subcutaneously (sc)
to rats 30 min before each of three experimental sessions.
3
As illustrated in
Figure 15.8B, 1mg kg
1
of PHA-543613 significantly improved the ability of
the test subjects to discriminate between the novel and familiar objects after a
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