Focusing on autism symptoms masks sex-specific needs of autistic children: An example from the Sydney Child Neurodevelopment Research Registry.

Studies have shown that there is a difference between biological sex at birth in autism spectrum disorder. There remains a lack of understanding about how the symptoms of autism differ between assigned males at birth and assigned females at birth. We looked at the presence of sex differences in a large group of autistic toddlers, children and adolescents, who were seen in a large diagnosis and assessment clinic.

Adolescent alcohol binge drinking and withdrawal: behavioural, brain GFAP-positive astrocytes and acute methamphetamine effects in adult female rats.

Rationale: Alcopop beverages are generally the first alcoholic beverage that young females drink which contain high levels of sugar and alcohol. The over-consumption of these drinks may encourage alcohol co-administration with methamphetamine (METH) impacting on drinking behaviour and glial function.

Aims: The aims of this study were to evaluate the effect of adolescent binge alcohol exposure on consumption level, anxiety-like behaviour, cross-sensitization with METH and on astrocyte expression in reward related brain regions.

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.

Differential effects of GABA receptor activation in the prelimbic and orbitofrontal cortices on anxiety.

Rationale: The development of effective anxiety treatments has been hindered by limited understanding of the neurobiological mechanisms involved in anxiety regulation. Whilst gamma-aminobutyric acid (GABA) neurotransmission in the prefrontal cortex (PFC) is one mechanism consistently implicated in anxiety regulation, PFC subregions may contribute uniquely.

Objectives: The present study examined the effects of inactivating the PFC subregions of the prelimbic cortex (PrL) or orbitofrontal cortex (OFC) through GABA receptor (GABAR) activation, on anxiety behaviours in male Wistar rats.

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 L-type calcium channel blocker, isradipine, attenuates cue-induced cocaine-seeking by enhancing dopaminergic activity in the ventral tegmental area to nucleus accumbens pathway.

Previous preclinical and clinical investigations have focused on the L-type calcium channel (LTCC) as a potential therapeutic target for substance abuse. While some clinical studies have examined the ability of LTCC blockers to alter cocaine's subjective effects, very few LTCC studies have examined cocaine relapse. Here, we examined whether ventral tegmental area (VTA)-specific or systemic administration of the LTCC inhibitor, isradipine, altered cocaine-seeking behavior in a rat model.

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.

Regional c-Fos expression induced by peripheral oxytocin administration is prevented by the vasopressin 1A receptor antagonist SR49059.

Peripherally administered oxytocin induces a wide range of behavioural and physiological effects that are thought to be mediated by the oxytocin receptor (OTR). However, oxytocin also has considerable affinity for the vasopressin 1A receptor (VR), such that various oxytocinergic effects may in fact be mediated by the VR rather than the OTR. Here we used c-Fos immunohistochemistry to determine the extent to which the regional pattern of neuronal activation produced by peripheral oxytocin involves the VR.

The neurocircuitry involved in oxytocin modulation of methamphetamine addiction.

The role of oxytocin in attenuating the abuse of licit and illicit drugs, including the psychostimulant methamphetamine, has been examined with increased ferocity in recent years. This is largely driven by the potential application of oxytocin as a pharmacotherapy. However, the neural mechanisms by which oxytocin modulates methamphetamine abuse are not well understood.

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.

Adolescent pre-treatment with oxytocin protects against adult methamphetamine-seeking behavior in female rats.

The neuropeptide oxytocin (OT), given acutely, reduces self-administration of the psychostimulant drug methamphetamine (METH). Additionally, chronic OT administration to adolescent rats reduces levels of alcohol consumption in adulthood, suggesting developmental neuroplasticity in the OT system relevant to addiction-related behaviors. Here, we examined whether OT exposure during adolescence might subsequently inhibit METH self-administration in adulthood.

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.

Oxytocin modulates dopamine-mediated reward in the rat subthalamic nucleus.

The subthalamic nucleus (STh) is increasingly recognized as an important region involved in the motivation for drug reward. It is not yet known if dopamine, the neurotransmitter primarily responsible for reward signaling, is also involved in mediating reward-related activity in the STh. The neuropeptide oxytocin acts within the STh to reduce the rewarding effects of the psychostimulant methamphetamine, through a proposed interaction with dopamine.

Oxytocin directly administered into the nucleus accumbens core or subthalamic nucleus attenuates methamphetamine-induced conditioned place preference.

Accumulating evidence indicates that the neuropeptide oxytocin (OXY) may modulate reward-related behavioural responses to methamphetamine (METH) administration. Limited research has examined the effect of OXY on METH-induced conditioned place preference (CPP) and little is known about the neural mechanisms involved. A Fos immunohistochemistry study recently demonstrated that peripheral OXY administration reduced METH-induced Fos expression within the nucleus accumbens (NAc) core and subthalamic nucleus (STh) in rats.