Protracted abstinence in males with an opioid use disorder: partial recovery of nucleus accumbens function

Abstract

Opioid use disorder (OUD) affects more than 27 million people globally accounting for more than 300,000 deaths annually. Protracted abstinence among individuals with OUD is rare due to a high relapse rate among those not receiving medications for OUD. Extensive preclinical studies form the basis of the allostasis theory, which proposes long-lasting functional brain abnormalities that persist after opioid withdrawal and contribute to relapse. Few studies have tested the allostasis theory in humans using neuroimaging. Here, we used fMRI and an instrumental learning task to test allostasis theory predictions (ATP) of functional abnormalities in both positive valence (PVS) and negative valence (NVS) accumbens systems in OUD patients with protracted abstinence (n = 15), comparing them with OUD patients receiving methadone treatment (MT) (n = 33), and with healthy controls (n = 23). As hypothesized, protracted abstinence OUD patients showed incomplete recovery of nucleus accumbens function, as evidenced by the blunted response to aversive events (NVS) during negative reinforcement, as observed in MT patients. In contrast, their accumbens response to rewarding events (PVS) during positive reinforcement was similar to that of controls and different from that in MT patients whose response was blunted. Protracted abstinence OUD patients also showed improvements in depression symptoms compared to MT patients. Residual depressive symptoms and pre-MT intravenous drug measures were associated with worse accumbens function in protracted abstinence. These results support the ATP of long-lasting dysfunction of NVS after withdrawal and show preliminary evidence of recovery of PVS function with protracted withdrawal. Therapeutic strategies that target NVS may facilitate recovery.

Blunted midbrain reward activation during smoking withdrawal: a preliminary study

“…For the present study, we used an instrumental reward learning and loss avoidance learning task that we have used for studies on depressive illnesses ( Johnston et al, 2015 ), opioid dependency ( Gradin et al, 2014 ; Tolomeo et al, 2022 ), and binge alcohol drinking ( Tolomeo et al, 2020 ; 2023 ). Subjects had to learn to choose between two pairs of nonsmoking-related visual stimuli to maximise rewards and avoid losses.…”

“…Subjects had to learn to choose between two pairs of nonsmoking-related visual stimuli to maximise rewards and avoid losses. The events of interest were the times when the subjects learnt the outcomes of their decisions, e.g., “you win” or “nothing.” As described in a series of previous studies, this contrast provides a non-invasive measure of brain reward function ( Steele et al, 2007 ; Gradin et al, 2014 ; Johnston et al, 2015 ; Tolomeo et al, 2022 ). It is important to note that the reward signal at the outcome time is different from the signal at the time the pairs of stimuli are presented, and a choice has to be made, the latter being the expected reward value signal ( Tolomeo et al, 2023 ).…”

“…Figure 1 shows the reward–gain and loss avoidance instrumental learning task used during fMRI ( Tolomeo et al, 2020 ; Tolomeo et al, 2022 ). Before scanning, all participants had a brief training session on the task on a PC, which used different stimuli from those used in the scanner.…”

Maternal Childhood Maltreatment, Internal Working Models, and Perinatal Substance Use: Is There a Role for Hyperkatifeia? A Systematic Review

“… 41 Thus, even in the absence of acute withdrawal, associations between relief from negative affect and prior substance use constitute a powerful ongoing motivationally salient stimulus for continued use. 183 , 184 Given this notion of addiction as both a reward deficit and stress surfeit problem, it is highly likely that both childhood maltreatment experiences and subsequent intimate partner violence further impact this process. 39 - 42 To the extent that these traumatic experiences pre-date substance use initiation, people may experience more brittle affect and emotional dysregulation at baseline.…”

Abnormal cerebral metabolism and metabolic connectivity in individuals with heroin dependence: an integrated resting-state PET/fMRI study in large-scale networks

“…Heroin addiction is characterized by excessive drug-seeking and drug-taking behaviours despite serious adverse consequences, and it manifests clinically as a chronic relapsing cycle of binging, intoxication, withdrawal and craving. [1][2][3] Functional magnetic resonance imaging (fMRI) studies have demonstrated an association between specific forms of addiction (e.g., substance use and behavioural) and abnormal func-tional connectivity between and within brain networks. 4,5 Among these addiction-related networks, a triple brain network comprising the default mode network (DMN), the salience network (SN) and the executive control network (ECN), which was proposed by Menon, 6 has received extensive attention in the context of heroin addiction.…”