Can the incentive-sensitization theory of addiction incorporate addiction to opioid drugs?

The Incentive Sensitization Theory (IST) of addiction posits that repeated intermittent exposure to potentially addictive drugs can sensitize brain mesolimbic dopamine systems. Those systems normally attribute incentive salience to rewards and their cues, but when sensitized may produce compulsive cue-triggered 'wanting' for drugs that can persist long after the discontinuation of drug use and the cessation of withdrawal symptoms, thus contributing to an enduring propensity to relapse. Much of the original evidence for IST came from studies on psychostimulant drugs, such as amphetamine and cocaine. But can IST account for addiction to opioid drugs as well? Several serious objections have been raised as to whether pathological 'wanting' for opioids involves dopamine sensitization, as posited by IST, thus suggesting IST does not apply to opioid addiction. Here we assess those objections and provide a review of evidence from the opioid literature on both human and non-human animals relevant to IST. We first summarize the main tenets of IST and the major objections to IST regarding opioid use disorder and addiction. We then address the following specific questions. (1) Do opioid drugs engage mesolimbic systems, including dopamine? (2) Do opioid drugs sensitize those dopamine systems? (3) Do opioid drugs also sensitize the incentive motivational effects of drugs and their cues, to produce incentive-sensitization and excessive 'wanting'? (4) Is dopamine necessary for opioid self-administration. We conclude that the answer to the question posed in the title of this paper is 'yes', even though there remain significant gaps in this literature that need to be filled by future studies.