Blockade of the Dopamine D3 Receptor Attenuates Opioids-Induced Addictive Behaviours Associated with Inhibiting the Mesolimbic Dopamine System / 神经科学通报·英文版

Opioid use disorder (OUD) has become a considerable global public health challenge; however, potential medications for the management of OUD that are effective, safe, and nonaddictive are not available. Accumulating preclinical evidence indicates that antagonists of the dopamine D3 receptor (D3R) have effects on addiction in different animal models. We have previously reported that YQA14, a D3R antagonist, exhibits very high affinity and selectivity for D3Rs over D2Rs, and is able to inhibit cocaine- or methamphetamine-induced reinforcement and reinstatement in self-administration tests. In the present study, our results illustrated that YQA14 dose-dependently reduced infusions under the fixed-ratio 2 procedure and lowered the breakpoint under the progressive-ratio procedure in heroin self-administered rats, also attenuated heroin-induced reinstatement of drug-seeking behavior. On the other hand, YQA14 not only reduced morphine-induced expression of conditioned place preference but also facilitated the extinguishing process in mice. Moreover, we elucidated that YQA14 attenuated opioid-induced reward or reinforcement mainly by inhibiting morphine-induced up-regulation of dopaminergic neuron activity in the ventral tegmental area and decreasing dopamine release in the nucleus accumbens with a fiber photometry recording system. These findings suggest that D3R might play a very important role in opioid addiction, and YQA14 may have pharmacotherapeutic potential in attenuating opioid-induced addictive behaviors dependent on the dopamine system.

Association of opioid use disorder with outcomes of hospitalizations for acute myocardial infarction in the United States

Abstract Objective While Opioid Use Disorder (OUD) has been linked to inferior clinical outcomes, studies examining the clinical outcomes and readmission of OUD patients experiencing Acute Myocardial Infarction (AMI) remain lacking. The authors analyze the clinical and financial outcomes of OUD in a contemporary cohort of AMI hospitalizations. Methods All non-elective adult (≥ 18 years) hospitalizations for AMI were tabulated from the 2016‒2019 Nationwide Readmissions Database using relevant International Classification of Disease codes. Patients were grouped into OUD and non-OUD cohorts. Bivariate and regression analyses were performed to identify the independent association of OUD with outcomes after non-elective admission for AMI, as well as subsequent readmission. Results Of an estimated 3,318,257 hospitalizations for AMI meeting study criteria, 36,057 (1.1%) had a concomitant diagnosis of OUD. While OUD was not significantly associated with mortality, OUD patients experienced superior cardiovascular outcomes compared to non-OUD. However, OUD was linked to increased odds of non-cardiovascular complications, length of stay, costs, non-home discharge, and 30-day non-elective readmission. Conclusions Patients with OUD presented with AMI at a significantly younger age than non-OUD. While OUD appears to have a cardioprotective effect, it is associated with several markers of increased resource use, including readmission. The present findings underscore the need for a multifaceted approach to increasing social services and treatment for OUD at index hospitalization.

Relationship of Probable Attention Deficit Hyperactivity Disorder with Severity of Psychopathology and Impulsivity in a Sample of Male Patients with Opioid Use Disorder

OBJECTIVE: The aim of the present study was to evaluate relationship of probable attention deficit hyperactivity disorder (ADHD) with severity of psychopathology and the effect of impulsivity on this relationship in a sample of male patients with opioid use disorder (OUD). METHODS: Participants included 234 patients (115 inpatients and 119 outpatients) with OUD. Participants were evaluated with the Adult ADHD Self-Report Scale (ASRS-v1.1), the Symptom Checklist-90-R (SCL-90-R) and the Short Form of Barratt Impulsiveness Scale (BIS-11-SF). RESULTS: Psychopathology and impulsivity scores were higher among those with the probable ADHD. ADHD scores were midly to moderately correlated with impulsivity and psychopathology scores. In logistic regression analyses, while severity of general psychopathology and impulsivity predicted probable ADHD in the first Model, in the second Model, among dimensions of psychopathology obsessive compulsive (OC) dimension, whereas among dimensions of impulsivity non-planning and motor impulsivity predicted probable ADHD. CONCLUSION: These findings suggest that probable ADHD is related with the severity of psychopathology, particularly OC dimension, while the severity of impulsivity may have an partial mediator (particularly non-planning and motor impulsivity) effect on this relationship among patients with OUD.

An overview on the opioid substitution therapy service model / 中华流行病学杂志

When facing the worldwide abuse of opioid substance,one of the effective responses is opioid substitution therapy (OST).However,different OST service patterns may affect the therapeutic outcome.Using the System Engineering Initiative for Patient Safety (SEIPS) model,we can analyze the factors that affecting the outcomes of patients from the perspective work system.In this paper,SEIPS model is used to describe the existing OST service model.According to the operation mechanism of the methadone maintenance treatment in China and the existing OST service model,some suggestions are put forward to carry out effective OST service in the country.

An overview on the opioid substitution therapy service model / 中华流行病学杂志

When facing the worldwide abuse of opioid substance,one of the effective responses is opioid substitution therapy (OST).However,different OST service patterns may affect the therapeutic outcome.Using the System Engineering Initiative for Patient Safety (SEIPS) model,we can analyze the factors that affecting the outcomes of patients from the perspective work system.In this paper,SEIPS model is used to describe the existing OST service model.According to the operation mechanism of the methadone maintenance treatment in China and the existing OST service model,some suggestions are put forward to carry out effective OST service in the country.