Abstract
Background
Contemporary learning theories of drug addiction ascribe a key role to Pavlovian learning
mechanisms in the development, maintenance, and relapse of addiction. In fact, cue-reactivity
research has demonstrated the power of alcohol-associated cues to activate the brain’s
reward system, which has been linked to craving and subsequent relapse. However, whether
de novo Pavlovian conditioning is altered in alcohol use disorder (AUD) has rarely
been investigated.
Methods
To characterize de novo Pavlovian conditioning in AUD, 62 detoxified patients with
AUD and 63 matched healthy control participants completed a Pavlovian learning task
as part of a Pavlovian-to-instrumental transfer paradigm during a functional magnetic
resonance imaging session. Patients were followed up for 12 months to assess drinking
behavior and relapse status.
Results
While patients and healthy controls did not differ in their ability to explicitly
acquire the contingencies between conditioned and unconditioned stimuli, patients
with AUD displayed significantly stronger amygdala responses toward Pavlovian cues,
an effect primarily driven by stronger blood oxygen level–dependent differentiation
during learning from reward compared with punishment. Moreover, in patients compared
with controls, differential amygdala responses during conditioning were positively
related to the ability of Pavlovian stimuli to influence ongoing instrumental choice
behavior measured during a subsequent Pavlovian-to-instrumental transfer test. Finally,
patients who relapsed within the 12-month follow-up period showed an inverse association
between amygdala activity during conditioning and relapse latency.
Conclusions
We provide evidence of altered neural correlates of de novo Pavlovian conditioning
in patients with AUD, especially for appetitive stimuli. Thus, heightened processing
of Pavlovian cues might constitute a behaviorally relevant mechanism in alcohol addiction.
Keywords
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Article info
Publication history
Published online: February 15, 2023
Accepted:
February 3,
2023
Received in revised form:
February 3,
2023
Received:
October 21,
2022
Publication stage
In Press Corrected ProofIdentification
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© 2023 Published by Elsevier Inc. on behalf of Society of Biological Psychiatry.
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