42.01
The effects of chronic phencyclidine treatment on prepulse inhibition in rats;
ultrasonic vocalisations reveal fear conditioning
Neuronal
Networks
Laboratory
Beth Tunstall, Dr Simon Beckett and Dr Rob Mason
School of Biomedical Sciences, Queen’s Medical Centre, Nottingham, UK
INTRODUCTION:
RESULTS:
SUMMARY:
• Deficits in prepulse inhibition (PPI: a diminished response to a
second tone if preceded almost immediately by a first) are considered
a cardinal symptom of schizophrenic-like symptoms in humans[1].
 The chronic dosing regime
described here produced a deficit in
PPI response up to two days after
the final PCP treatment compared to
• Acute PCP treatment has been used to successfully mimic this deficit
in non-human primates [2] and rats [3], however, to date, very few
chronic PCP treatment regimen have produced long term deficits in
PPI [4].
saline controls, which persisted for a
further three days.
 Interestingly, the saline treated
• Adult rats emit calls in two main frequency ranges; ~22 kHz calls in
response to aversive stimuli [5]~ 50 kHz calls in response to
rewarding stimuli [6]. Acute PCP effects both the types and structures
of the calls emitted by adult rats [7].
AIMS:
• To establish a chronic dosing schedule using PCP in juvenile
Sprague- Dawley rats and confirm its efficacy using prepulse
inhibition as a measure of sensory gating ability compared to
saline treated controls
• To examine the USVs produced at the end of chronic treatment
with PCP or saline in order to establish whether the structure of
USVs can be used as a predictive measure of PCP induced
psychotic-like behaviour as confirmed by prepulse inhibition
testing.
group showed a deficit in PPI
performance five days after the last
treatment, which may be explained
by inadvertent fear conditioning.
Figure 2: The deficit in PPI
(A) Was significantly greater in PCP pre- treated
animals (n=10) on day sixteen.
(B) Saline pre-treated animals (n = 10) showed a
greater deficit than PCP pre-treated animals.
(C) Within group comparisons showed that saline
pre-treated animal show deficit in PPI
performance on day 19 compared to 16.
(D) There was no overall change in the PPI
response of the PCP pre-treated animals
between test days suggesting chronic effects
of PCP administration.
Figure 3: The interval between the stimulus
presentation and the first call
Figure 4: The duration of the first six calls
emitted after each type of startle pulse
Increased corticotropin- releasing
(A) Was significantly shorter in animals pretreated with PCP (n=7) on day sixteen compared
to saline (n=8).
(A) Was unchanged between day sixteen and
nineteen in saline (n=8) pre-treated animals
performance [8].
(B) Was significantly shorter in animals pretreated with PCP on day nineteen compared to
saline.
(C) and (D) Within group comparison revealed this
interval was significantly increased in both
saline (C) and PCP (D) pre-treated animals on
day nineteen compared to day sixteen.
(B) Was significantly shorter in the PCP (n=7)
group (n=7)
factor has been shown to inhibit PPI
 The number and duration of the ’22
kHz’ calls produced during the PPI
testing revealed that this paradigm
(C) Within group comparison showed that saline
pre-treated animals had significantly longer
call duration after stimulus on day nineteen
compared to sixteen.
(D) There was no significant difference in the PCP
pre-treated animals.
induced anxiety in rats from both the
PCP treatment group and the saline
controls. Specifically, the duration,
calling period and time to onset of
calling reveal that a level of fear
conditioning had taken place in
saline treated animals which had not
METHODS:
For Figure 1 to 3, all data are presented as means ± SEM and analysed using a two-way ANOVA with post hoc Bonferroni tests when
significance reached 95%.P < 0.01 (**)
affected the PCP treated group.
These data suggest that PPI can act as
Male Sprague-Dawley rats were treated once a day for 14 days
with either PCP (5mg.kg-1 i.p., n=10) or saline (1ml.kg-1i.p., n=10)
from 30 days old. Acoustic startle response (ASR) was tested on
day 0, and PPI on day 16 and 19 (Figure 1). USVs were recorded
during testing with an Ultrasound Gate (Customised model 112,
Avisoft, DE), and analysed post hoc (v 4.38 SASLab-Pro, Avisoft,
DE). Statistical analyses were carried out using Prism (v 4
Graphpad, USA). PPI data were analysed using a Two-way ANOVA
with Bonferroni post hoc tests when significance reached 95%.
a measure of deficits in working
memory as well as of sensory gating.
REFERENCES &
ACKNOWLEDGEMENTS:
[1] Perry W & Braff DL. (1994), “Information-processing deficits and
thought disorder in schizophrenia”, Am. J. Psychiatry., vol. 151,
no. 3, pp. 363-367.
[2] Javitt, D. & Lindsley, R. (2001), Psychopharmacology, vol. 156,
no. 2 - 3, pp. 165-168.
[3] Wiley, J. I., Harvey S.A, Balster R.L, & Nicholson, K. L. (2003),
Psychopharmacology 165, 378-385.
Figure 5: Calling periods over the course of PPI testing.
The grey section of the bars indicates the acclimation period and the white section, the
test period. The left hand black bar indicates the onset of calling, and the right hand
bar, the extinction.
(A) There was no significant difference in calling period between groups in day sixteen.
Figure 1: The time course in days of the experiment.
The percentage of prepulse inhibition was calculated as:

 mean( pulse _ alone )  mean( prepulse )  
% PPI  100  100 * 
 
mean( pulse _ alone )



(B) There was a significant increase in the calling period of PCP pre-treated animals
(n=7) when compared to the saline group (n=8) on day nineteen.
Data are presented as mean ± SEM. P < 0.01, ** using an unpaired t
test.
Figure 6: The number of 22 kHz calls produced on each day
[4] Wang, C., McInnis, J., West, J. B., Bao, J., Anastasio, N., Guidry,
J. A., Ye, Y., Salvemini, D., & Johnson, K. M. (2003), J.
(A) There was a significant decrease on day nineteen in saline pre-treated
animals (n=8).
Pharmacol. Exp Theraputics, vol. 304, no. 1, pp. 266-271.
[5] Brudzynski, S. M. (2001), Neurosci Biobehav Rev. vol. 25, no. 78, pp. 611-617.
(B) This was not reflected in the PCP group (n=7).
[6] Burgdorf, J., Knutson, B., & Panksepp, J. (2000), Behav
Data are presented as mean ± SEM, and analysed using Wilcoxon matched
pairs test, P < 0.05 *.
Neurosci, vol. 114, no. 2, pp. 320-327.
[7] B. Tunstall, R. Mason, S.R.G. Beckett, T. Shackleton (2003), Soc.
Neurosci. Abs Program No. 627.3.
[8] Conti, L., Murray J, Ruiz, M., & Printz, M. (2002),
Psychopharmacology, vol. 161, no. 3, pp. 296-303.
Beth Tunstall was funded by an MRC studentship.