Biology Reference
In-Depth Information
inhibitors to a variety of other CNS diseases, including Alzheimer's disease,
Parkinson's disease, Huntington's disease, attention-deficit hyperactivity disorder,
schizophrenia, stroke, autism, and tardive dyskinesia (Cheng et al.
2010
; Titus et al.
2008
; Millar et al.
2007
).
PDE4A and PDE4D may be important in the mediation of antidepressant
activity and memory, while PDE4B is more likely involved in dopamine-associated
and stress-related processes. This is supported by studies showing that PDE4D is
important in antidepressant-like behavior, whereas PDE4B appears to be involved in
signaling pathways important for schizophrenia and anxiety (Zhang et al.
2002a
,
b
,
2008
; Millar et al.
2005
; Siuciak et al.
2007
) (Figs.
3
and
4
).
Rolipram is a selective inhibitor of PDE4 and increases intracellular cAMP by
inhibiting its hydrolysis (Houslay et al.
2005
). Research investigating PDE4 func-
tion using rolipram suggests that, given peripherally, rolipram elevates cAMP
levels in the brain and enhances retention in passive avoidance tasks in mice,
which is consistent with the concept that cAMP is related to neural processes that
underlie learning and memory (Zhang et al.
2000
,
2005
; Rutten et al.
2006
).
Subsequent studies have shown the positive effects of PDE4 inhibition on other
types of memory, such as working and reference memory and contextual fear
memory (Gong et al.
2004
; Zhang and O'Donnell
2000
). Working memory refers
to processes encoding items related to the temporal/personal context of a single
event or a test situation, while reference memory encodes context-independent
a
200
150
*
*
100
50
Fig. 3 PDE4D
mice
exhibited antidepressant-like
behavior in the tail-
suspension and forced-swim
tests. (a) The immobility
duration in the tail suspension
test. (b) The immobility
duration in the forced swim
test in the PDE4D
þ
/
þ
,
PDE4D+/
and PDE4D
/
mice. Values shown are mean
SEM;
*
p
<
0.05,
**
/
0
+/+
+/-
-/-
b
200
150
100
** #
50
p
<
0.01 vs. PDE4D
þ
/
þ
;
#
p
<
0.05 vs. PDE4D
þ
/
(
n
¼
7). Reprinted with
permission from (Zhang et al.
2002a
)
0
+/+
+/-
-/-
Genotypes
