Authors: Nathalie VANHILLE1, Aude BELIN-RAUSCENT2, Adam MAR3, Eric DUCRET4* and David BELIN2*

High locomotor reactivity to novelty is associated with an increased propensity to choose saccharin over cocaine: new insights into the vulnerability to addiction

1INSERM CIC-1403, Université de Poitiers, Ecole Doctorale Biosanté, 1 rue Georges Bonnet, 86000 Poitiers

2 Department of Pharmacology, University of Cambridge. Tennis Court Road, Cambridge CB2 1PD, UK

3 Department of Psychology, Behavioural and Clinical Neuroscience Institute, University of Cambridge, Downing Street, CB2 3EB, Cambridge, UK.

4 INSERM & Université de Poitiers, Pôle Biologie Santé, 1 rue Georges Bonnet, 86000 Poitiers

*: these authors contributed equally to this study

Correspondance should be addressed to:

Dr David Belin,

Department of Pharmacology,

University Of Cambridge, Tennis Court Road

CB2 1PD Cambridge, UK.

e-mail:

SOM Results

The behavioural cost of the two manipulandum may not be equivalent as pressing a lever and turning a wheel may not be as effortful. Thus, a difference in response requirment for cocaine and saccharin may alter the demand for these reinforcers and bias the choice made by the animals. Therefore, any effect of the manipulandum on the operant responding was controlled by training a second cohort of rats (n=12) with reversed contingencies: cocaine was infused after turning the wheel and saccharin was delivered following a lever-press. Animals displayed similar acquisition of the two instrumental tasks (type of reinforcer effect F(1, 10)=58.012, p<0.001; interaction reinforcer x time effect F(9, 90)=1.41, p=0.197) and progressively reached the maximal saccharin intake per session (time effect F(9, 90)=5.35, p<0.001). Furthermore, the two cohorts of rats differed neither in the number of responses for cocaine or saccharin nor in the volume of sweet water consumed per session.

SOM Figures

Figure s1: Interindividual differences in novelty-induced locomotor activity, autoshaping and anxiety are not overlapping.

Locomotor response to a novel environment was neither predicted by (a) the level of anxiety or (b) the propensity to approach the reward (GT) or its associated CS (ST). Furthermore, (c) high (HR) and low (LR) responders spent a similar amount of time in the open arms of the elevated plus maze as did the goal- (GT) and sign-trackers (ST). Finally, (c) HR and LR were not dissociable on the basis of their autoshaping behaviour nor did (d) low (LA) and high anxious (HA) rats.

Figure s2: Preference for cocaine does not depend upon the nature of the instrumental response to obtain the rewards.

Rats trained to turn a wheel to obtain cocaine and to press a lever to gain access to saccharin (a) acquired both instrumental responses at a similar rate as compared with animals trained with reversed contingencies and (b) learnt to optimize their saccharin consumption. Furthermore, (c) these rats also preferred cocaine over saccharin.

SOM Tables

Table s1: Summary of the behavioural phenotypes and their associated tests and measures.

Table s2: Matrix of the dimensional relationships between the various behaviours measured.

R values displayed in blue were associated with p < 0.05.