Emerging medications and pharmacological treatment approaches for substance use disorders.

Medications to treat substance use disorders remain suboptimal or, in the case of stimulants and cannabis, non-existent. Many factors have contributed to this paucity, including the biological complexity of addiction, regulatory challenges, and a historical lack of enthusiasm among pharmaceutical companies to commit resources to this disease space. Despite these headwinds, the recent opioid crisis has highlighted the devastating consequences of SUDs for both individuals and society, stimulating urgent efforts to identify novel treatment approaches.

Sex differences in the social motivation of rats: Insights from social operant conditioning, behavioural economics, and video tracking.

Background: Social behaviour plays a key role in mental health and wellbeing, and developing greater understanding of mechanisms underlying social interaction-particularly social motivation-holds substantial transdiagnostic impact. Common rodent behavioural assays used to assess social behaviour are limited in their assessment of social motivation, whereas the social operant conditioning model can provide unique and valuable insights into social motivation. Further characterisation of common experimental parameters that may influence social motivation within the social operant model, as well as complementary methodological and analytical approaches, are warranted.

Effects of CB1 receptor negative allosteric modulator Org27569 on oxycodone withdrawal symptoms in mice.

Rationale/objectives: Targeting cannabinoid receptor type 1 (CB1R) has shown promise for treating opioid withdrawal symptoms. This study aimed to investigate the efficacy of a specific CB1R negative allosteric modulator (NAM), Org27569, in reducing both naloxone-precipitated and protracted withdrawal symptoms in oxycodone-dependent mice.

Methods: Mice received escalating doses of oxycodone (9-33 mg/kg IP) or saline twice daily for 9 days, followed by a final dose of oxycodone (33 mg/kg) or saline in the morning of day 9.

Quiet wakefulness: the influence of intraperitoneal and intranasal oxytocin on sleep-wake behavior and neurophysiology in rats.

Study Objectives: Exogenous administration of the neuropeptide oxytocin exerts diverse effects on various neurobehavioral processes, including sleep and wakefulness. Since oxytocin can enhance attention to social and fear-related environmental cues, it should promote arousal and wakefulness. However, as oxytocin can attenuate stress, reduce activity, and elicit anxiolysis, oxytocin might also prime the brain for rest, and promote sleep.

The effect of self-administered methamphetamine on GABAergic interneuron populations and functional connectivity of the nucleus accumbens and prefrontal cortex.

Introduction: Methamphetamine (METH, "ice") is a potent and addictive psychostimulant. Abuse of METH perturbs neurotransmitter systems and induces neurotoxicity; however, the neurobiological mechanisms which underlie addiction to METH are not fully understood, limiting the efficacy of available treatments. Here we investigate METH-induced changes to neuronal nitric oxide synthase (nNOS), parvalbumin and calretinin-expressing GABAergic interneuron populations within the nucleus accumbens (NAc), prefrontal cortex (PFC) and orbitofrontal cortex (OFC).

Oxytocin as an adolescent treatment for methamphetamine addiction after early life stress in male and female rats.

Early life stress (ELS) is associated with perturbed neural development and augmented vulnerability to mental health disorders, including addiction. How ELS changes the brain to increase addiction risk is poorly understood, and there are no therapies which target this ELS-induced vulnerability. ELS disrupts the oxytocin system, which can modulate addiction susceptibility, suggesting that targeting the oxytocin system may be therapeutic in this ELS-addiction comorbidity.

Cannabidiol but not cannabidiolic acid reduces behavioural sensitisation to methamphetamine in rats, at pharmacologically effective doses.

Rationale: Cannabidiol (CBD) and cannabidiolic acid (CBDA) are non-psychoactive components of the cannabis plant. CBD has been well characterised to have anxiolytic and anticonvulsant activity, whereas the behavioural effects of CBDA are less clear. Preclinical and clinical data suggests that CBD has antipsychotic properties and reduces methamphetamine self-administration in rats.

The effect of adolescent social isolation on vulnerability for methamphetamine addiction behaviours in female rats.

Rationale: Stress exposure during adolescence contributes to developing a methamphetamine (METH) use disorder. However, most of the studies investigating addiction-related behaviours include only male rodents, despite METH addiction rates being higher in females. Furthermore, animal studies investigating the effects of stress on methamphetamine addiction have used only basic self-administration models which may not be sensitive to the effects of stress.

Adolescent oxytocin administration reduces depression-like behaviour induced by early life stress in adult male and female rats.

Early life stress (ELS) exposure alters brain development, increasing vulnerability for mental illness in adulthood, including depression. Despite this association, there are no approved pharmacotherapies to protect against the emergence of mental illness resulting from ELS. Recent preclinical work showed that oxytocin (OT) administration in adulthood reduced depressive-like behaviour in male rats with a history of ELS.

Sign tracking predicts cue-induced but not drug-primed reinstatement to methamphetamine seeking in rats: Effects of oxytocin treatment.

Background: The incentive sensitisation theory of addiction posits that drug-associated stimuli become imbued with incentive motivational properties, driving pathological drug seeking. However, pre-existing variability in the incentive salience to non-drug reward cues ('sign trackers' (STs); 'goal trackers' (GTs)) is also predictive of the desire for and relapse to cocaine and opioids. Here, we asked whether variation in propensity to attribute incentive salience to a food cue is predictive of reinstatement to the highly addictive psychostimulant methamphetamine (METH), and whether treatment with the promising anti-addiction therapy oxytocin differentially reduces METH behaviour between STs and GTs.

Maternal separation changes maternal care, anxiety-like behaviour and expression of paraventricular oxytocin and corticotrophin-releasing factor immunoreactivity in lactating rats.

The early postnatal period is a time of tremendous change for the dam and her offspring. During this time, environmental insults such as repeated stress exposure can have detrimental effects. In research that has focused on the effect of postnatal stress exposure on the dams, conflicting changes in maternal care and anxiety-like behaviour have been reported.

The vagus nerve mediates the suppressing effects of peripherally administered oxytocin on methamphetamine self-administration and seeking in rats.

The neuropeptide oxytocin has emerged as a promising pharmacotherapy for methamphetamine (METH) addiction, and clinical trials of intranasal oxytocin are underway. However, there is debate as to how peripherally administered oxytocin alters brain signalling to modulate addiction processes. Interestingly, there is evidence for functional interactions between peripheral oxytocin administration and the vagus nerve.

The effect of chronic oxytocin treatment during abstinence from methamphetamine self-administration on incubation of craving, reinstatement, and anxiety.

Methamphetamine (METH) abuse is characterised by chronic relapse and anxiety, for which there are no effective pharmacotherapies. Acute treatment with the neuropeptide oxytocin has shown therapeutic potential for METH addiction and has social and anxiolytic effects in METH-naïve rats. However, the effects of chronic oxytocin treatment in METH-experienced rats are unknown.

Cannabidiol treatment reduces the motivation to self-administer methamphetamine and methamphetamine-primed relapse in rats.

Background: Methamphetamine is an addictive stimulant that can cause many adverse physical, psychological and psychosocial effects. Preliminary evidence shows cannabidiol, a non-intoxicating constituent of the cannabis plant, may have efficacy in treating opioid and nicotine dependence. However, no study has yet examined whether cannabidiol treatment might impact on methamphetamine addiction.

The impact of early life stress on the central oxytocin system and susceptibility for drug addiction: Applicability of oxytocin as a pharmacotherapy.

Early life trauma is strongly associated with an increased vulnerability to abuse illicit drugs and the impairment of neural development. This includes alterations to the development of the oxytocin system, which plays a pivotal role in the regulation of social behaviours and emotion. Dysregulation of this important system also contributes to increased susceptibility to develop drug addiction.

The role of the vasopressin V1A receptor in oxytocin modulation of methamphetamine primed reinstatement.

The neuropeptide oxytocin has shown promise as an effective therapy in pre-clinical models of methamphetamine (METH) addiction. The nucleus accumbens core (NAcc) has been identified as an important site for oxytocin to inhibit METH behaviours, although previous findings suggest that the effects of oxytocin in the NAcc are mediated by receptors other than the oxytocin receptor (OTR). Oxytocin has high affinity for the vasopressin V1A receptor (V1AR) which has been implicated in numerous oxytocin-dependent social behaviours.

The Involvement of Oxytocin in the Subthalamic Nucleus on Relapse to Methamphetamine-Seeking Behaviour.

The psychostimulant methamphetamine (METH) is an addictive drug of abuse. The neuropeptide oxytocin has been shown to modulate METH-related reward and METH-seeking behaviour. Recent findings implicated the subthalamic nucleus (STh) as a key brain region in oxytocin modulation of METH-induced reward.

Oxytocin in the nucleus accumbens core reduces reinstatement of methamphetamine-seeking behaviour in rats.

The psychostimulant methamphetamine (METH) is an addictive illicit drug. Systemic administration of the neuropeptide oxytocin modulates METH-related reward and METH-seeking behaviour. Recent findings demonstrated a reduction in METH-induced reward by oxytocin administration into the nucleus accumbens (NAc) core.