Responsiveness to drug cues and natural rewards in opiate addiction: associations with later heroin use

Arch Gen Psychiatry. 2009 Feb;66(2):205-12. doi: 10.1001/archgenpsychiatry.2008.522.


Context: Although drug cues reliably activate the brain's reward system, studies rarely examine how the processing of drug stimuli compares with natural reinforcers or relates to clinical outcomes.

Objectives: To determine hedonic responses to natural and drug reinforcers in long-term heroin users and to examine the utility of these responses in predicting future heroin use.

Design: Prospective design examining experiential, expressive, reflex modulation, and cortical/attentional responses to opiate-related and affective stimuli. The opiate-dependent group was reassessed a median of 6 months after testing to determine their level of heroin use during the intervening period.

Setting: Community drug and alcohol services and a clinical research facility.

Participants: Thirty-three opiate-dependent individuals (mean age, 31.6 years) with stabilized opiate-substitution pharmacotherapy and 19 sex- and age-matched healthy non-drug users (mean age, 30 years).

Main outcome measures: Self-ratings, facial electromyography, startle-elicited postauricular reflex, and event-related potentials combined with measures of heroin use at baseline and follow-up.

Results: Relative to the control group, the opiate-dependent group rated pleasant pictures as less arousing and showed increased corrugator activity, less postauricular potentiation, and decreased startle-elicited P300 attenuation while viewing pleasant pictures. The opiate-dependent group rated the drug-related pictures as more pleasant and arousing, and demonstrated greater startle-elicited P300 attenuation while viewing them. Although a startle-elicited P300 amplitude response to pleasant (relative to drug-related) pictures significantly predicted regular (at least weekly) heroin use at follow-up, subjective valence ratings of pleasant pictures remained the superior predictor of use after controlling for baseline craving and heroin use.

Conclusions: Heroin users demonstrated reduced responsiveness to natural reinforcers across a range of psychophysiological measures. Subjective rating of pleasant pictures robustly predicted future heroin use. Our findings highlight the importance of targeting anhedonic symptoms within clinical treatment settings.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Affective Symptoms / physiopathology
  • Affective Symptoms / psychology
  • Affective Symptoms / rehabilitation
  • Alcoholism / physiopathology
  • Alcoholism / psychology
  • Alcoholism / rehabilitation
  • Arousal / drug effects
  • Arousal / physiology
  • Attention* / physiology
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / physiopathology
  • Comorbidity
  • Cues*
  • Electromyography
  • Emotions / drug effects
  • Emotions / physiology
  • Event-Related Potentials, P300 / drug effects
  • Event-Related Potentials, P300 / physiology
  • Female
  • Follow-Up Studies
  • Heroin Dependence / physiopathology
  • Heroin Dependence / psychology*
  • Heroin Dependence / rehabilitation
  • Humans
  • Male
  • Middle Aged
  • Motivation*
  • Narcotics / therapeutic use
  • Recurrence
  • Reflex, Startle / drug effects
  • Reflex, Startle / physiology
  • Reward*
  • Risk Factors
  • Young Adult


  • Narcotics