Pavlovian to Instrumental Transfer Responses Do Not Correlate With Addiction-Like Behavior in Rats.

Tatiane T. Takahashi,Rainer Spanagel,Thomas Enkel,Sara Reithofer,Valentina Vengeliene

doi:10.3389/fnbeh.2019.00129

Abstract

Pavlovian learning plays a prominent role in the etiology of addiction. The influence of Pavlovian conditioning on the expression of an instrumental response can be studied using the Pavlovian-to-instrumental transfer (PIT) paradigm. This paradigm consists of independent Pavlovian conditioning and instrumental training prior to the combination of both during the test. During this test, the reward is not available, and an increase in the instrumental responding during conditioned stimuli presentation is a measure of PIT. Recent studies have reported a higher PIT in alcohol and nicotine dependent patients, suggesting that enhanced PIT might be a marker for dependence vulnerability. However, these studies did not use standard PIT procedures, and a clear correlation between an enhanced PIT and drug-related and addictive behaviors has so far not been demonstrated. For a systematic evaluation rats were trained in a cocaine addiction model. Addicted-like and non-addicted-like rats were subsequently assessed in the PIT paradigm. In a further experiment, rats were first tested in the PIT paradigm and thereafter subjected to cocaine self-administration (CSA) training. Our results revealed that addicted-like rats did not differ from non-addicted-like in their performance in the PIT test. However, CSA behavior showed a positive correlation with PIT. This data suggests that stronger PIT may predict higher motivational impact of conditioned stimuli on drug self-administration and improved learning of drug-cue association rather than the risk to develop addiction as such.

Highlights

Addiction theories postulate that Pavlovian learning plays a key role in the development of drug addiction and maintenance of drug use
Our results show that animals used for the establishment of the Pavlovian-to-instrumental transfer (PIT) paradigm increased lever responding during the conditioned stimulus (CS) presentations of the PIT test (factor condition: F(1,120) = 16.2, p < 0.001) compared to the pre-CS condition
Three-way analysis of variance (ANOVA) revealed that lever-responding was different during the CS presentation between animals which received Pavlovian conditioning sessions (PIT group) and animals that were prevented from learning stimulus-reward association during

Summary

Introduction

Addiction theories postulate that Pavlovian learning plays a key role in the development of drug addiction and maintenance of drug use. Pavlovian learning involves transfer of the motivational value of the primary reward to the conditioned stimulus (CS) associated with drug availability during the course of drug use (Berridge and Robinson, 2003; Sanchis-Segura and Spanagel, 2006). Such a CS can impact on ongoing instrumental behavior, even if the instrumental behavior is acquired independently of Pavlovian conditioning. Pavlovian conditioned cues can bias instrumental behavior towards drug seeking and intake in both drug abusers and animals trained to self-administer drugs (Everitt et al, 2001; Glasner et al, 2005; Weiss, 2005; Hogarth et al, 2007; LeBlanc et al, 2012). It is well established that drug conditioned cues play a critical role in drug addiction the role of PIT on drug-related and addictive behaviors is less clear (Hogarth et al, 2018)

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