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.

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.

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.

Jason B. Tanenbaum1, Lisa M. Bollwage1 and Anthony S. Rauhut 1,2, Department of Psychology1 and Neuroscience Program2, Dickinson College, Carlisle, PA

References

DiscussionAbstractThe 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.

The 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.

Only highest nicotine dose (0.8 mg/kg) yielded a CTA in the Wistar

rats.

Collectively, these results suggest that the WKY rats are more

responsive to the avoidance properties of nicotine relative to the

Wistar rats.

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).

Prediction

Introduction Previous research suggests that Wistar Kyoto rats are an animal

model of clinical depression, exhibiting less motor activity and

greater anhedonia compared to other rat strains (Pare, 2000).

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.

Purpose

The purpose of the present study was to examine if WKY rats were

less responsive to the avoidance properties of nicotine compared

to Wistar rats, as assessed by the conditioned taste avoidance

(CTA) paradigm.

Methods

Results

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.

Wistar Kyoto and Wistar Rats Differ in Nicotine-Induced Conditioned Taste Avoidance

Acclimation

5 Days

Pretest

1 Session

15 min access to saccharin (0.15 %)

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

Consumption Data

Weight Data

Acknowledgements

24 h

24 h

48 h after last drug session

Test

15 min access to saccharin (0.15%) in the absence of any injections

1. Cailhol, S. & Mormède, P. (2001) Conditioned taste aversion and

alcohol drinking: Strain and gender differences. Journal of Studies

on Alcohol, 63, 91-99.

2. Paré, W.P. (2000). Investigatory behavior of a novel conspecific by

wistar kyoto, wistar, spraugue-dawley rats. Brain Research Bulletin,

53, 759-765.

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.

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.

WKY

1 2 3 4 Pre-Test Test 0

50

100

150

200

250

300

Vehicle0.2 mg/kg0.4 mg/kg0.8 mg/kg

Drug Session

Wei

ght (

g)

Nicotine Dose

WISTAR

1 2 3 4 Pre-Test Test 0

50

100

150

200

250

300

Vehicle0.2 mg/kg0.4 mg/kg0.8 mg/kg

Nicotine Dose

Drug Session

Wei

ght (

g)

Initial Water Restriction1 Session

15 min access to tap water following water removal

24 h

WKY Wistar

1 2 3 4 Pre-Test Test 0

4

8

12

16

20

Vehicle0.2 mg/kg0.4 mg/kg0.8 mg/kg

Nicotine Dose*

WKY

#

Drug Session

Co

nsu

mp

tio

n (

ml)

1 2 3 4 Pre-Test Test 0

5

10

15

20

25

30

Vehicle0.2 mg/kg0.4 mg/kg0.8 mg/kg

Nicotine Dose

WISTAR

*

Drug Session

Co

nsu

mp

tio

n (

ml)

* *#