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Wistar Kyoto and Wistar Rats Differ in Nicotine-Induced Conditioned Taste Avoidance
Abstract
The Wistar-Kyoto (WKY) rat is an animal model of clinical
depression. Previous research in the laboratory suggests that WKY
rats are less responsive to the rewarding and locomotor effects of
nicotine compared to Wistar rats. Such strain differences may be
due to general, non-specific strain differences in the
neuropharmacological processing of nicotine. Thus, the present
experiment examined if WKY rats were less responsive to another
neuropharmacological aspect of nicotine compared to Wistar rats.
Specifically, the present study examined if WKY rats were less
responsive to the avoidance properties of nicotine compared to
Wistar rats, as assessed using the conditioned taste avoidance
(CTA) paradigm. WKY and Wistar rats underwent a CTA procedure
which consisted of 4 alternating drug and non-drug sessions
(counterbalanced). Drug sessions consisted of 15-min access to
saccharin (0.15%) followed immediately by an injection (s.c.) of
either vehicle (physiological saline) or nicotine (0.2, 0.4 or 0.8
mg/kg). It was found that WKY rats that received the lowest nicotine
dose (0.2 mg/kg) did not differ from WKY rats that received the
vehicle (i.e., no CTA). However, WKY rats that received the two
highest nicotine doses (0.4 and 0.8 mg/kg) drank less than the WKY
rats that received the vehicle on several sessions (i.e., CTAs). Only
the Wistar rats that received the highest nicotine dose (0.8 mg/kg)
drank less than Wistar rats that received the vehicle on several
sessions. Thus, WKY rats were more responsive to the avoidance
properties of nicotine compared to Wistar rats.
and Anthony S. Rauhut
1,2,
Department of
1
Psychology
Purpose
and Neuroscience
2
Program ,
Dickinson College, Carlisle, PA
Results
Discussion
 The
 The purpose of the present study was to examine if WKY rats were
20
 Only highest nicotine dose (0.8 mg/kg) yielded a CTA in the Wistar
30
WISTAR
WKY
Prediction
If WKY rats are unresponsive to the behavioral actions of
nicotine, then WKY rats are predicted to display a less robust
CTA relative to Wistar rats.
If, however, WKY rats are responsive to the behavioral
actions of nicotine, then WKY rats are predicted to display a
CTA similar to or more than Wistar rats.
present experiment found that nicotine dose-dependently
produced a CTA in WKY rats. Specifically, the two highest nicotine
doses (0.4 and 0.8 mg/kg) yielded a CTA whereas the lowest nicotine
dose (0.2 mg/kg) did not.
Consumption Data
less responsive to the avoidance properties of nicotine compared
to Wistar rats, as assessed by the conditioned taste avoidance
(CTA) paradigm.
rats.
 Collectively,
25
16
12
#
*
8
*
#
*
Nicotine Dose
Vehicle
0.2 mg/kg
0.4 mg/kg
0.8 mg/kg
4
Consumption (ml)
Lisa M.
1
Bollwage
Consumption (ml)
Jason B.
1
Tanenbaum ,
these results suggest that the WKY rats are more
responsive to the avoidance properties of nicotine relative to the
Wistar rats.
20
15
*
10
Nicotine Dose
Vehicle
0.2 mg/kg
0.4 mg/kg
0.8 mg/kg
5
0
0
Pre-Test 1
2
3
4
Test
Pre-Test 1
Drug Session
2
3
4
Test
Drug Session
Left Panel. The two highest nicotine doses (0.8 and 2.0 mg/kg)
produced a CTA on several sessions and the test session in the WKY rats.
(* = 0.8 mg/kg nicotine vs. vehicle; # = 0.4 mg/kg nicotine vs. vehicle), p <
.05.
WKY
Right Panel. The highest nicotine dose (0.8 mg/kg) produced a CTA on
the test session only in the Wistar rats (* = 0.8 mg/kg nicotine vs. vehicle),
p < .05.
Wistar
 These results are consistent with prior studies that have shown that
WKY rats are responsive to other drugs of abuse (e.g., alcohol;
Cailhol and Morméde, 2001).
 Moreover, these results suggest that the previously-observed deficit
in nicotine conditioned place preference by the WKY rats is not due to
a general, unresponsiveness to the behavioral actions of nicotine or a
general deficit in learning.
 Rather, the results of the present experiment, when viewed in tandem
with the results of previous unpublished research from the laboratory,
indicate that WKY rats display a specific deficit in reward-based
learning with respect to nicotine.
 This interpretation is consistent with previous studies suggesting that
WKY display anhedonia under certain conditions (Jiao, Pare, and
Tejani-Butt, 2003; Pare, 2000).
Methods
5 Days
 Previous research suggests that Wistar Kyoto rats are an animal
 Previous unpublished research from the laboratory has found that
WKY rats failed to display a nicotine conditioned place preference
or show alterations in nicotine-induced changes in locomotor
activity compared to Wistar rats. These results suggest that WKY
rats are less responsive to the rewarding and locomotor properties
of nicotine compared to Wistar rats.
 However,
the finding that WKY rats failed to display a nicotine
conditioned place preference or nicotine-induced alterations in
locomotor activity may suggest that WKY rats were unresponsive
to any behavioral actions of nicotine.
24 h
Initial Water Restriction
1 Session
15 min access to tap water following water removal
2. Paré, W.P. (2000). Investigatory behavior of a novel conspecific by
wistar kyoto, wistar, spraugue-dawley rats. Brain Research Bulletin,
53, 759-765.
24 h
Pretest
3. Xilu, J., Paré, W.P., & Butt-Tejani, S. (2003). Strain differences in the
distribution of dopomine transporter sites in rat brain. Progress in
Neuro-Psychopharmacology & Biological Psychiatry, 27, 913-919.
Weight Data
1 Session
15 min access to saccharin (0.15 %)
300
300
WKY
24 h
Conditioning
8 Sessions—Alternating Drug and NonDrug Sessions
(counterbalanced)
Drug Sessions: 15 min access to saccharin (0.15%) followed
immediately by an injection (s.c) of vehicle (physiological saline) or
nicotine (0.2, 0.4 or 0.8 mg/kg)
NonDrug Sessions: 15 min access to tap water in the absence of any
injections
WISTAR
250
250
200
200
Weight (g)
model of clinical depression, exhibiting less motor activity and
greater anhedonia compared to other rat strains (Pare, 2000).
1. Cailhol, S. & Mormède, P. (2001) Conditioned taste aversion and
alcohol drinking: Strain and gender differences. Journal of Studies
on Alcohol, 63, 91-99.
Weight (g)
Introduction
References
Acclimation
150
100
50
0
Test
15 min access to saccharin (0.15%) in the absence of any
injections
Nicotine Dose
Vehicle
0.2 mg/kg
0.4 mg/kg
0.8 mg/kg
50
0
Pre-Test 1
2
3
Drug Session
48 h after last drug session
150
100
Nicotine Dose
Vehicle
0.2 mg/kg
0.4 mg/kg
0.8 mg/kg
Acknowledgements
4
Test
Pre-Test 1
2
3
4
Test
Drug Session
Left Panel. Displays weights of WKY rats over 6 sessions. No significant
group differences were observed, p > 0.05.
Right Panel. Displays weights of Wistar rats over 6 sessions. Although
no individual group differences existed, Wistar rats were heavier and
gained more weight over time compared to WKY rats, ps < 0.05.
This research was supported by a National Institutes of
Health grant (DA019866), awarded to A. S. Rauhut.
We would like to especially thanks Professor Rauhut
for his guidance and support during this experiment.