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

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 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 to 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.Publisher PDFPeer reviewe

Dysfunction of the prefrontal cortex in addiction: neuroimaging findings and clinical implications”,

Drug addiction encompasses a relapsing cycle of intoxication, bingeing, withdrawal and craving that results in excessive drug use despite adverse consequences (FIG. 1). Drugs that are abused by humans increase dopamine in the reward circuit and this is believed to underlie their rewarding effects. Therefore, most clinical studies in addiction have focused on the midbrain dopamine areas (the ventral tegmental area and substantia nigra) and the basal ganglia structures to which they project (the ventral striatum, where the nucleus accumbens is located, and the dorsal striatum), which are known to be involved in reward, conditioning and habit formation On the basis of imaging findings and emerging preclinical studies 5,6 , we proposed 10 years ago that disrupted function of the PFC leads to a syndrome of impaired response inhibition and salience attribution (iRISA) in addiction Here we review imaging studies into the role of the PFC in addiction from the past decade, integrating them into the iRISA model with the aim to gain a greater understanding of the dysfunction of the PFC in addiction. Specifically, this is the first systematic evaluation of the role of distinct regions within the functionally heterogeneous PFC in the neuropsychological mechanisms that putatively underlie the relapsing cycle of addiction. We review positron emission tomography (PET) and functional MRI (fMRI) studies focusing on regions of the PFC that have been implicated in addiction. These include the orbitofrontal cortex (OFC), anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex (DLPFC) (see R E V I E W S Non-contingent administration Administration of a certain drug that is not dependent on the subject's behaviour. Fixed-rate self-administration Self-administration of a certain drug on a ratio between drug delivery and behaviour that is fixed by an experimenter (for example, after emission of a certain number of responses or after a certain time has elapsed following the previous response). into the executive function of the PFC we refer the reader to other reviews Direct effects of drug exposure Here, we review studies that assessed the effects of stimulant and non-stimulant drugs on PFC activity 18 Fluorodyoxyglucose PET (PET FDG) study, administration of the stimulant drug methylphenidate (MPH) to active cocaine users increased whole-brain glucose metabolism 14 . Here, the left lateral OFC showed greater metabolism in response to unexpected than to expected MPH; the opposite pattern to that of the BOLD effect in the above study 13 possibly reflects the different temporal sensitivity of the imaging modalities (see below). Stimulant drugs also increase PFC activity in laboratory animals. For example, regional cerebral blood flow (rCBF) in drug-naive rhesus monkeys increased in DLPFC after non-contingent administration and in ACC during a simple fixed-rate self-administration of cocain