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Oestrogen modulation of the effect of 8-OH-DPAT on prepulse inhibition: effects of aromatase deficiency and castration in mice.
[aromatase deficiency]
The
aim
of
this
study
was
to
investigate
the
interaction
of
sex
steroid
hormones
,
particularly
oestrogen
,
in
the
regulation
of
prepulse
inhibition
(
PPI
)
by
serotonin-
1
A
(
5
-
HT
1
A
)
receptors
.
We
studied
aromatase
knockout
(
ArKO
)
mice
,
which
are
unable
to
produce
oestrogen
but
have
high
levels
of
testosterone
,
and
the
effects
of
castration
.
Treatment
of
male
ArKO
mice
with
the
5
-
HT
1
A
receptor
agonist
,
8
-
hydroxy-dipropyl-aminotetralin
(
8
-
OH
-DPAT
)
,
caused
an
increase
in
PPI
that
was
significantly
greater
than
in
male
wild-
type
controls
.
Castration
of
male
mice
caused
a
significant
enhancement
of
the
effect
of
8
-
OH
-DPAT
in
control
mice
;
however
,
there
was
no
change
in
the
effect
of
this
drug
in
ArKO
mice
.
There
was
no
significant
effect
of
8
-
OH
-DPAT
on
PPI
in
either
female
ArKO
or
wild-
type
controls
.
In
all
experiments
,
the
effects
of
8
-
OH
-DPAT
on
startle
were
not
different
between
the
groups
.
[
3
H
]
8
-
OH
-DPAT
autoradiography
showed
no
differences
in
5
-
HT
1
A
receptor
binding
densities
in
areas
of
the
forebrain
,
hippocampus
or
raphe
region
that
could
explain
the
PPI
results
.
These
data
show
that
the
absence
of
oestrogen
in
male
ArKO
mice
leads
to
a
greater
effect
of
5
-
HT
1
A
receptor
stimulation
on
PPI
.
This
effect
can
be
mimicked
in
male
control
mice
by
castration
.
The
differential
involvement
of
oestrogen
and
testosterone
in
these
animal
models
is
discussed
.
