Slide sem t

1
CONTEXT FEAR CONDITIONING INHIBITS ACTIVE
DEFENSIVE BEHAVIOR ELICITED BY ELECTRICAL
STIMULATION OF DORSAL PERIAQUEDUCTAL GRAY
RELATIONSHIP BETWEEN ANXIETY AND PANIC
ATTACK J.Landeira-Fernandez1,2
R.L.Nogueira2,4 V.Magierek3 P.L.Ramos2
N.G.Silveira-Filho3 1. Departamento de
Psicologia, PUC/RIO, Rio de Janeiro, Brazil 2.
Curso de Psicologia, Universidade Estacio de Sa,
Rio de Janeiro, Brazil 3. Departamento de
Psicobiologia, Universidade de Sao Paulo, Sao
Paulo, Brazil 4. Curso de Psicologia,
Universidade de Ribeirao Preto, Ribeirao Preto,
Brazil
INTRODUCTION Different patterns of animal
defensive behaviors have been employed as useful
tools for investigating and understanding the
underlying mechanisms for different anxiety
disorders. Accordingly, flight behavior evoked by
electrical stimulation of the dorsal portion of
the periaqueductal gray (DPAG) has been proposed
as a model of panic attacks (5,6), whereas
freezing response to contextual cues previously
associated with electrical footshocks as an
animal model of anxiety. The present study
employed these two animals to investigate the
relationship between anxiety and panic attack.
This is an important issue since experiments with
human patients have lead to conflicting results.
There are evidences supporting the view that
anxiety might either facilitate or inhibit the
occurrence of panic attack. METHODS Male
albino Wistar rats were anaesthetized and a
bipolar electrode was implanted into the DPAG.
Five days after the surgery, each animal was
placed inside the experimental chamber for a 6
min habituation period. After that, DPAG was
electrically stimulated in order to determine the
animals DPAG aversive baseline threshold to
evoke a vigorous escape response. Following the
DPAG electrical stimulation, one group of animals
(DPAG/SHOCK) was submitted to the context fear
conditioning procedure. Conditioning consisted in
the presentation of 5 unsignaled two-sec 1 mA
electrical footshocks with a 1 min intershock
interval. A no-shock control group (DPAG/NO
SHOCK) had exactly the same procedure as the
first group with the exception that no footshock
was delivered. Testing session took place two
hours later. During this phase, all animals were
reexposed to the experimental chamber and
freezing behavior was recorded for 5 min.
Freezing behavior was scored through a
time-sample procedure. For each 2 s, an
experimenter, who was blind to the experimental
conditions, rated the animal's behavior as
freezing or activity. Freezing was defined as
absence of visible body movements, except the
activity necessary for respiration. After the
freezing scoring period, a new DPAG aversive
threshold to induce an escape response was
determined. At the end of the experiment, animals
were sacrificed and the brains were removed for
histological analysis.
DISCUSSION Results from the present
experiment clearly indicate that contextual cues
previously associated with footshock induced
defensive freezing behavior and inhibited active
defensive reaction evoked by electrical
stimulation of the DPAG. Since context fear
conditioning is a model of anxiety whereas
electrical stimulation of the DPAG is related to
panic attack, it is concluded that an increase in
anxiety might cause a decrease in panic attack.
In accordance with this view, it has been
reported that relaxation therapy employed to
reduce anxiety symptoms may precipitate panic
attacks. Moreover, the frequency of panic attacks
is higher at the beginning of agoraphobia, when
there is little anticipatory anxiety, as compared
with the late phase, when anxiety has fully
developed. Pharmacological results also support
the suggestion that enhancement of anxiety
inhibits the occurrence of panic attacks. Panic
disorder patients treated with serotonergic
reuptake blocking drugs show a decrease in panic
attack but an increase in anxiety. Therefore, it
appears that activation of neural circuitry
involved in anxiety might in fact inhibit the
incidence of panic attacks.
RESULTS A representative histological section
showing the location of the electrode tip is
presented in Figure 1. Histological examination
of the brain slices indicated that all electrode
tips were located inside or at the borders of
DPAG.
A- AVERSIVE CONTEXT CONDITIONING
B- ELECTRICAL CURRENT THRESHOLD
Figure 1- Photomicrograph showing a typical
example of a stimulation electrode site (arrow).
Aq, aqueduct of Sylvius DPAG, dorsal
periaqueductal gray DlPAG, dorsolateral
periaqueductal gray VlPAG, ventrolateral
periaqueductal gray VPAG, ventral periaqueductal
gray. The histological section was located 7.6 mm
posterior to bregma.
Figure 2a presents the mean ( SEM) of freezing
behavior during the 5-min testing session 2 hours
after rats were exposed (DPAG / SHOCK) or not
(DPAG / NO SHOCK) to 5 unsignaled footshocks. The
results are clear cut and indicate that animals
exposed to contextual cues that were previously
associated with electrical footshocks displayed
more freezing than control non-shocked animals
(t(20)5,8 plt0.001). The high levels of freezing
among the animals in the DPAG/SHOCK group is in
accordance with previous findings which report
that unsignaled footshock reliably leads to
context fear conditioning (7). Figure 2b presents
the mean ( SEM) change in DPAG electrical
current aversive threshold between test and
baseline phases of the experiment. As can be
observed, current threshold difference (D)
between testing and baseline phases was greater
among animals previously exposed contextual cues
previously associated with electrical footshocks
when compared to no-shock control group (t(20)
2,3 plt0,05). The fact that DPAG/NO SHOCK group
presented a negative D-threshold indicates that
some animals in this group presented a lower
current aversive threshold during the test phase
as compared to their baseline aversive threshold.
The opposite pattern was observed among the
animals in the DPAG/SHOCK group. Therefore, these
results indicate that context fear conditioning
was able to inhibit active flight reactions
evoked by electrical stimulation of the DPAG.
Acknowledgements This work was supported by CNPq
(Proc. No. 94/5933-2), University of Estácio de
Sá (UNESA), University of Riberão Preto (UNAERP)
and AFIP.
Figure 2- (A) Mean percent ( SEM) of time
spent engaged in freezing behavior during testing
session 2 hours after rats were exposed (DPAG /
SHOCK) or not exposed (DPAG / NO SHOCK) to 5
unsignaled footshocks. (B) Mean ( SEM) of the
difference (D) between testing and baseline DPAG
electrical current threshold to induce an escape
behavior. plt0.05.