ORCID Profile
0000-0002-9938-1936
Current Organisation
UNSW Sydney
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Publisher: Elsevier BV
Date: 02-2013
DOI: 10.1016/J.YHBEH.2012.12.003
Abstract: 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 meth hetamine, through a proposed interaction with dopamine. However, the mechanisms of this interaction are unclear. The current study aimed to determine whether (i) dopamine microinjected into the STh would result in a significant place preference following a single-trial conditioning session, (ii) co-administered dopamine receptor antagonist would block the formation of a conditioned place preference (CPP) for dopamine, (iii) co-administered oxytocin would prevent CPP for dopamine and (iv) whether the selective oxytocin antagonist desGly-NH(2),d(CH(2))(5)[D-Tyr(2),Thr(4)]OVT, when co-administered with oxytocin and dopamine, would reverse the effects of oxytocin and result in a CPP for dopamine. Results showed that male Sprague Dawley rats i) formed a preference for the context paired with dopamine (100 nmol/side) administration into the STh, which was prevented by co-administration of ii) the mixed dopamine receptor antagonist fluphenazine (10 nmol/side) or iii) oxytocin (0.6 pmol/side), [corrected] with the oxytocin effect on dopamine CPP reversed by the co-administration of the oxytocin receptor antagonist (3 nmol/side). These data suggest that dopamine neurotransmission in the STh produces rewarding effects that can be reduced by activation of local oxytocin receptors.
Publisher: Springer Science and Business Media LLC
Date: 17-05-2022
DOI: 10.1038/S41386-022-01336-Y
Abstract: 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. Therefore, we determined whether adolescent oxytocin treatment after ELS could: (1) reduce vulnerability to anxiety, social deficits, and meth hetamine-taking and reinstatement and (2) restore hypothalamic oxytocin and corticotropin-releasing factor expressing neurons and peripheral oxytocin and corticosterone levels. Long Evans pups underwent maternal separation (MS) for either 15 min or 360 min on postnatal days (PND) 1–21. During adolescence (PNDs 28–42), rats received a daily injection of either oxytocin or saline. In Experiment 1, adult rats were assessed using the elevated plus-maze, social interaction procedure, and meth hetamine self-administration procedure, including extinction, and cue-, meth hetamine- and yohimbine-induced reinstatement. In Experiment 2, plasma for enzyme immunoassays and brain tissue for immunofluorescence were collected from adult rats after acute stress exposure. Adolescent oxytocin treatment ameliorated ELS-induced anxiety and reduced meth hetamine- and yohimbine-induced reinstatement in both sexes, and suppressed meth hetamine intake and facilitated extinction in males only. Additionally, adolescent oxytocin treatment after ELS restored oxytocin-immunoreactive cells and stress-induced oxytocin levels in males, and attenuated stress-induced corticosterone levels in both sexes. Adolescent oxytocin treatment reverses some of the ELS effects on later-life psychopathology and vulnerability to addiction.
Publisher: Springer Science and Business Media LLC
Date: 03-08-2022
DOI: 10.1007/S00213-022-06175-9
Abstract: Meth hetamine (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). We hypothesise that dysfunction or loss of these GABAergic interneuron populations may disrupt the excitatory/inhibitory balance within the brain. Male Long Evans rats ( N = 32) were trained to lever press for intravenous METH or received yoked saline infusions. Following 14 days of behavioural extinction, animals were given a non-contingent injection of saline or METH (1 mg/kg, IP) to examine drug-primed reinstatement to METH-seeking behaviours. Ninety minutes post-IP injection, animals were culled and brain sections were analysed for Fos, nNOS, parvalbumin and calretinin immunoreactivity in eight distinct subregions of the NAc, PFC and OFC. METH exposure differentially affected GABAergic populations, with METH self-administration increasing nNOS immunoreactivity at distinct locations in the prelimbic cortex and decreasing parvalbumin immunoreactivity in the NAc. METH self-administration triggered reduced calretinin immunoreactivity, whilst acute METH administration produced a significant increase in calretinin immunoreactivity. As expected, non-contingent METH-priming treatment increased Fos immunoreactivity in subregions of the NAc and PFC. Here we report that METH exposure in this model may alter the function of GABAergic interneurons in more subtle ways, such as alterations in neuronal firing or synaptic connectivity.
Publisher: Elsevier BV
Date: 08-2019
DOI: 10.1016/J.PBB.2019.06.002
Abstract: Addiction to the psychostimulant Meth hetamine (METH) is characterised by high rates of relapse. Currently there are no approved effective pharmacotherapies for METH dependence. The neuropeptide oxytocin (OXY) potently reduces METH-seeking behaviours in rodent models of relapse and is now being used in clinical trials to treat drug-dependent in iduals. However, OXY administration in humans may be impeded by its poor penetration of the brain. Therefore, identification of the neural mechanisms by which OXY reduces METH relapse may guide the development of improved OXY-based therapies for METH addiction. Systemic OXY administration is associated with attenuated METH-induced activity in the prelimbic cortex (PrL) a key brain region which exerts control over much of the reward and addiction circuitry. However, it is not known whether OXY acts directly in the PrL to cause reductions in drug-seeking and downstream brain activity. Therefore, the present study sought to determine whether OXY infused into the PrL reduces cue-induced and METH-primed reinstatement and METH-induced neuronal activity in the downstream nucleus accumbens core (NAcc). Male Sprague Dawley rats underwent intravenous METH self-administration, extinction, and subsequent reinstatement tests. OXY was infused bilaterally into the PrL prior to cue-induced (0, 1 μg/side) and METH-primed reinstatement (0, 0.33, 1.0, 3.0 μg/side). Finally, we quantified cFos immunofluorescence in the NAcc as a proxy for downstream neuronal activity following a PrL infusion of OXY (0, 1 μg/side) prior to METH-primed reinstatement. OXY in the PrL significantly reduced both cue-induced and METH-primed reinstatement. Additionally, intra-PrL OXY reduced METH-induced cFos expression in the rostral but not caudal pole of the NAcc. These findings demonstrate OXY action in the PrL in reducing METH-seeking behaviours and METH-induced activity in the reward circuit. Furthermore, these results suggest that the therapeutic effects of systemically administered OXY on reducing METH-seeking behaviours may involve the PrL-NAc pathway.
Publisher: Wiley
Date: 04-2016
DOI: 10.1111/JNE.12337
Abstract: The neuropeptide oxytocin attenuates reward and abuse for the psychostimulant meth hetamine (METH). Recent findings have implicated the nucleus accumbens (NAc) core and subthalamic nucleus (STh) in oxytocin modulation of acute METH reward and relapse to METH-seeking behaviour. Surprisingly, the oxytocin receptor (OTR) is only modestly involved in both regions in oxytocin attenuation of METH-primed reinstatement. Coupled with the limited investigation of the role of the OTR in psychostimulant-induced behaviours, we primarily investigated whether there are cellular changes to the OTR in the NAc core and STh, as well as changes to oxytocin plasma levels, after chronic METH i.v. self-administration (IVSA) and after extinction of drug-taking. An additional aim was to examine whether changes to central corticotrophin-releasing factor (CRF) and plasma corticosterone levels were also apparent because of the interaction of oxytocin with stress-regulatory mechanisms. Male Sprague-Dawley rats were trained to lever press for i.v. METH (0.1 mg/kg/infusion) under a fixed-ratio 1 schedule or received yoked saline infusions during 2-h sessions for 20 days. An additional cohort of rats underwent behavioural extinction for 15 days after METH IVSA. Subsequent to the last day of IVSA or extinction, blood plasma was collected for enzyme immunoassay, and immunofluorescence was conducted on NAc core and STh coronal sections. Rats that self-administered METH had higher oxytocin plasma levels, and decreased OTR-immunoreactive (-IR) fibres in the NAc core than yoked controls. In animals that self-administered METH and underwent extinction, oxytocin plasma levels remained elevated, OTR-IR fibre density increased in the STh, and a trend towards normalisation of OTR-IR fibre density was evident in the NAc core. CRF-IR fibre density in both brain regions and corticosterone plasma levels did not change across treatment groups. These findings demonstrate that oxytocin systems, both centrally within the NAc core and STh, as well as peripherally through plasma measures, are dysregulated after METH abuse.
Publisher: Elsevier BV
Date: 03-2020
DOI: 10.1016/J.NEUBIOREV.2018.08.014
Abstract: 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. In this review, we provide an overview of the animal models of early life stress that are widely used, and discuss the impact that early life stress has on drug-taking behaviour in adolescence and adulthood in both sexes. We link this to the changes that early life stress has on the endogenous oxytocin system, and how exogenously administered oxytocin may help to re-establish functioning of the system, and in turn, reduce drug-taking behaviour.
Publisher: Elsevier BV
Date: 10-2016
DOI: 10.1016/J.BRAINRESBULL.2016.10.005
Abstract: 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 (V
Publisher: Springer Science and Business Media LLC
Date: 26-03-2022
DOI: 10.1007/S00213-022-06103-X
Abstract: Stress exposure during adolescence contributes to developing a meth hetamine (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 meth hetamine addiction have used only basic self-administration models which may not be sensitive to the effects of stress. This project explored whether adolescent isolation stress exposure increases the incidence of four key addiction-related behaviours in female rats. Thirty-two female rat pups were caged in groups of four or in idually during adolescence from postnatal (PND) day 22, with the latter being re-socialised in groups of four on PND 43. In adulthood, rats were tested for addiction-like behaviours in a METH self-administration paradigm modelling motivation to take METH, persistence in drug-seeking behaviour when METH was not available, resistance to extinction, and propensity to reinstate after a period of withdrawal. Adolescent social isolation resulted in lower METH intake during acquisition however, the paradigm modelling drug-seeking when the drug was unavailable engendered intermittent METH bingeing in all rats, abolishing the group differences in intake during this phase. Adolescent social isolation also accelerated extinction of non-reinforced lever pressing, and increased stress-primed reinstatement, compared to the group-housed rats. Adolescent social isolation stress alters various meth hetamine addiction-like behaviours in female rats.
Publisher: SAGE Publications
Date: 27-09-2018
Abstract: Meth hetamine 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 meth hetamine addiction. The current study investigated whether cannabidiol administration reduces the motivation to self-administer meth hetamine and relapse to meth hetamine-seeking behavior following abstinence. Thirty-two male Sprague Dawley rats with implanted jugular vein catheters were initially trained to self-administer meth hetamine via lever press during two-hour sessions on a fixed ratio 1 schedule of reinforcement. Rats in experiment 1 ( n=16) then advanced to a progressive ratio reinforcement schedule to examine the effects of cannabidiol (0, 20, 40, and 80 mg/kg intraperitoneal) on motivation to self-administer meth hetamine. Rats in experiment 2 ( n=16) were tested for cannabidiol effects on meth hetamine-primed reinstatement following extinction. Cannabidiol (80 mg/kg, but not 40 mg/kg, or 20 mg/kg) reduced the motivation to self-administer meth hetamine and attenuated meth hetamine-primed relapse to meth hetamine-seeking behavior after extinction. This is the first demonstration that cannabidiol can reduce the motivation to seek and consume meth hetamine, and suggests that cannabidiol might be worth trialing as a novel pharmacotherapy for meth hetamine dependence.
Publisher: Springer Science and Business Media LLC
Date: 18-04-2022
DOI: 10.1007/S00213-022-06119-3
Abstract: 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 meth hetamine self-administration in rats. An animal model that is commonly used to mimic the neurochemical changes underlying psychosis and drug dependence is meth hetamine (METH) sensitisation, where repeated administration of the psychostimulant progressively increases the locomotor effects of METH. The aim of this study was to determine whether CBD or CBDA attenuate METH-induced sensitisation of locomotor hyperactivity in rats. Eighty-six male Sprague Dawley rats underwent METH sensitisation protocol where they were subjected to daily METH (1 mg/kg on days 2 and 8, 5 mg/kg on days 3–7 i.p.) injections for 7 days. After 21 days of withdrawal, rats were given a prior injection of CBD (0, 40 and 80 mg/kg i.p.) or CBDA (0, 0.1, 10 and 1000 µg/kg i.p.) and challenged with acute METH (1 mg/kg i.p.). Locomotor activity was then measured for 60 min. Rats displayed robust METH sensitisation as evidenced by increased locomotor activity to METH challenge in METH-pretreated versus SAL-pretreated rats. CBD (40 and 80 mg/kg) reduced METH-induced sensitisation. There was no effect of any CBDA doses on METH sensitisation or acute METH-induced hyperactivity. These results demonstrate that CBD, but not CBDA, reduces METH sensitisation of locomotor activity in rats at pharmacologically effective doses, thus reinforcing evidence that CBD has anti-addiction and antipsychotic properties.
Publisher: Wiley
Date: 17-11-2016
DOI: 10.1111/ADB.12197
Abstract: The neuropeptide oxytocin (OT), given acutely, reduces self-administration of the psychostimulant drug meth hetamine (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. Female Sprague-Dawley rats were administered vehicle or OT (1 mg/kg, i.p.) once daily from postnatal days (PND) 28 to 37 (adolescence). At PND 62 (adulthood), rats were trained to self-administer METH (intravenous, i.v.) in daily 2-hour sessions for 10 days under a fixed ratio 1 (FR1) reinforcement schedule, followed by determination of dose-response functions (0.01-0.3 mg/kg/infusion, i.v.) under both FR1 and progressive ratio (PR) schedules of reinforcement. Responding was then extinguished, and relapse to METH-seeking behavior assessed following priming doses of non-contingent METH (0.1-1 mg/kg, i.p.). Finally, plasma was collected to determine pre-treatment effects on OT and corticosterone levels. Results showed that OT pre-treatment did not significantly inhibit the acquisition of METH self-administration or FR1 responding. However, rats pre-treated with OT responded significantly less for METH under a PR reinforcement schedule, and showed reduced METH-primed reinstatement with the 1 mg/kg prime. Plasma OT levels were also significantly higher in OT pre-treated rats. These results confirm earlier observations that adolescent OT exposure can subtly, yet significantly, inhibit addiction-relevant behaviors in adulthood.
Publisher: SAGE Publications
Date: 20-10-2020
Abstract: 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 meth hetamine (METH), and whether treatment with the promising anti-addiction therapy oxytocin differentially reduces METH behaviour between STs and GTs. Rats were trained to associate a Pavlovian cue with delivery of a sucrose pellet over 8 days. They then received jugular vein catheters for intravenous METH self-administration, followed by behavioural extinction, and cue-induced and METH-primed reinstatement to METH-seeking behaviours. Oxytocin was administered prior to self-administration and reinstatement tests. Despite the self-administration of similar amounts of METH, STs reinstated more to METH cues than did GTs, yet METH-priming reinstated STs and GTs similarly. Furthermore, oxytocin attenuated cue-induced reinstatement more so in STs than in GTs, and reduced METH-primed reinstatement to a greater extent in the top quartile of reinstaters, indicating that oxytocin treatment may be most effective for those at highest risk of addiction. This pre-existing bias towards reward cues presents a possible tool to screen for METH addiction susceptibility and may be useful for understanding the neurobiology of addiction and for pharmacotherapeutic discovery.
Publisher: Springer Science and Business Media LLC
Date: 03-05-2018
Publisher: Springer Science and Business Media LLC
Date: 14-07-2020
Publisher: Elsevier BV
Date: 08-2021
DOI: 10.1016/J.PNPBP.2021.110279
Abstract: 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. However, the ability of an OT treatment regime in adolescence, a critical developmental window for the OT system, to prevent the expression of depressive-like behaviours following ELS has not been investigated. Therefore, the present study aimed to determine whether chronic OT administration can ameliorate the enduring effects of ELS on depressive-like behaviours in both male and female rats. Following birth, Long Evans rat pups (N = 107) underwent maternal separation (MS) for either 15 min (MS15) or 6 h (MS360) on postnatal days (PND) 1-21. During adolescence (PND 28-42), rats received a daily injection of either OT (1 mg/kg) or saline. During adulthood (PND 57 onwards), effort-related motivation was measured using a model of effortful choice (EC), while behavioural despair was measured using the forced swim test (FST). Lastly, body and organ weights were measured to examine the physiological impacts of ELS and chronic OT administration. Overall, in both sexes, MS360 increased behavioural despair yet had no impact on effort-related motivation. Importantly, adolescent OT administration prevented the MS360-induced increase in behavioural despair in both males and females. Additionally, MS360 resulted in persistent reductions in body weight in both sexes post-weaning and increased spleen weight in males and adrenal weight in females. OT treatment had no impact on body weight in either sex, but prevented the MS-induced increase in adrenal gland weight in females. Overall, these findings have important implications for using oxytocin as a preventative pharmacotherapy after ELS.
Publisher: Wiley
Date: 16-11-2014
DOI: 10.1111/ADB.12198
Abstract: The psychostimulant meth hetamine (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. It is not known, however, if oxytocin acts in this region to reduce relapse to METH-seeking behaviour. Using the drug reinstatement paradigm in rats experienced at METH self-administration, we aimed to determine whether oxytocin pre-treatment within the NAc core would reduce relapse to METH use and if this could be reversed by the co-administration of the oxytocin receptor (OTR) antagonist desGly-NH2,d(CH2)5[D-Tyr2,Thr4]OVT. Male Sprague-Dawley rats underwent surgery to implant an intravenous jugular vein catheter and bilateral microinjection cannulae in the NAc core. Rats were then trained to self-administer intravenous METH (0.1 mg/kg/infusion) by lever press during 2-hour fixed ratio 1 scheduled sessions for 20 days. Following extinction of lever press activity, the effect of microinjecting saline, oxytocin (0.5 pmol, 1.5 pmol, 4.5 pmol) or co-administration of oxytocin (1.5 pmol) and desGly-NH2,d(CH2)5[D-Tyr2,Thr4]OVT (1 nmol, 3 nmol) in the NAc core (500 nl/side) was examined on METH-primed (1 mg/kg, i.p.) reinstatement of drug-seeking behaviour. Our results showed oxytocin directly administered into the NAc core decreased METH-primed reinstatement in a dose-dependent manner. Co-administration of the selective OTR antagonist did not specifically reverse the inhibitory effects of oxytocin on METH priming, suggesting mediation by receptors other than the OTR. These findings highlight an important modulatory effect of oxytocin in the NAc core on relapse to METH seeking.
Publisher: Wiley
Date: 06-2020
DOI: 10.1111/JNE.12861
Publisher: Society for Neuroscience
Date: 21-10-2020
Publisher: Elsevier BV
Date: 10-2022
DOI: 10.1016/J.NEUROPSYCHOLOGIA.2022.108366
Abstract: In iduals with Williams Syndrome (WS) or Downs Syndrome (DS) are often described as hypersociable, friendly and overly trusting of others. This hypersociability is a major concern for parents/caregivers due to the associated increased risk of exploitation and victimisation. Two brain regions - the amygdala and the orbitofrontal cortex (OFC) - have been implicated in driving this hypersociability in WS, and in the general population and have associations with emotional evaluation, threat detection and social motivation. However, there has been little neuroimaging research on this topic, especially in DS, to date. The aim of the present study was to investigate the potential neuroanatomical and neuropsychological correlates of hypersociability in WS and DS. Twelve in iduals with WS (M = 22 years of age) and eleven in iduals with DS (M = 26 years of age) completed a neuropsychological battery of executive functioning and social measures, including informant ratings on an ecologically measure of social approach. Clinical groups and twelve typically developing controls (M = 23 years) underwent a magnetic resonance imaging scan to investigate volumetric differences in the OFC and the amygdala. As expected, WS in iduals displayed the highest overall social approach, especially in relation to need to approach strangers and drive to interact with strangers, as well as inappropriate/overfriendly behaviours. Both groups rated similarly in terms of social trust and unconditional positive regard. Emotion recognition abilities were similar across groups, with the DS group displaying some difficulties with negative emotions (especially anger). Inhibition and flexibility were similarly impaired across WS and DS. Compared to neurotypical controls, the DS group showed increased amygdala volumes bilaterally, while the WS group showed an enlarged right medial OFC. Approach ratings were significantly correlated with left amygdala and medial and left lateral OFC volumes in WS, and with these same regions bilaterally in DS. Results provide potential biological explanations for the hypersociability seen in WS and DS. Future research should focus on other potential neural correlates, as well as potential genetic and hormonal contributions to approach.
Publisher: Springer Science and Business Media LLC
Date: 25-05-2020
Publisher: Elsevier BV
Date: 08-2020
Publisher: Springer Science and Business Media LLC
Date: 12-11-2019
Publisher: Public Library of Science (PLoS)
Date: 18-08-2015
Publisher: Elsevier BV
Date: 10-2016
DOI: 10.1016/J.YFRNE.2016.08.001
Abstract: The role of oxytocin in attenuating the abuse of licit and illicit drugs, including the psychostimulant meth hetamine, 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 meth hetamine abuse are not well understood. Recent research identified an important role for the accumbens core and subthalamic nucleus in this process, which likely involves an interaction with dopamine, glutamate, GABA, and vasopressin. In addition to providing an overview of meth hetamine, the endogenous oxytocin system, and the effects of exogenous oxytocin on drug abuse, we propose a neural circuit through which exogenous oxytocin modulates meth hetamine abuse, focusing on its interaction with neurochemicals within the accumbens core and subthalamic nucleus. A growing understanding of exogenous oxytocin effects at a neurochemical and neurobiological level will assist in its evaluation as a pharmacotherapy for drug addiction.
Publisher: Elsevier BV
Date: 03-2012
DOI: 10.1016/J.BBR.2011.11.038
Abstract: Accumulating evidence indicates that the neuropeptide oxytocin (OXY) may modulate reward-related behavioural responses to meth hetamine (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. The current study aimed to (i) investigate the effect of systemically administered OXY on METH-induced CPP, (ii) determine the effectiveness of a single-trial CPP procedure with METH, in order to (iii) evaluate whether pretreatment with OXY injected directly into the NAc core or the STh attenuates METH-induced CPP. Results showed that male Sprague Dawley rats learned to associate unique compartmental cues with METH (1 mg/kg, i.p.) such that they spent more time in the METH-paired compartment and less time in the saline-paired compartment. Pretreatment with systemic OXY (0.6 mg, i.p.), or OXY (0.6 ng, i.c.) microinjected into the NAc core or the STh prior to METH administration attenuated the formation of a CPP to METH. This provides further evidence that OXY acts within either the NAc core or the STh to reduce the rewarding effects of METH administration.
Publisher: Elsevier BV
Date: 05-2018
DOI: 10.1016/J.NEUROPHARM.2017.12.036
Abstract: The neuropeptide oxytocin has shown promise as an effective therapy in pre-clinical models of meth hetamine (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 aim of this study was to investigate the involvement of the V1AR in mediating the effect of oxytocin treatment to reduce METH-primed reinstatement of METH-seeking behaviour. Male rats were trained to self-administer intravenous infusions of METH by lever press during daily 2-h fixed ratio 1 scheduled sessions for 20 days. Following extinction of lever pressing, rats were tested for the effects of oxytocin alone, oxytocin co-administered with a selective V1AR antagonist, or oxytocin co-administered with a selective OTR antagonist, on METH-primed reinstatement, when administered systemically, or when microinjected into the NAcc. Systemic administration of oxytocin prevented METH-primed reinstatement, an effect which was significantly reduced by systemic pre-treatment with a V1AR but not OTR antagonist. Local administration of oxytocin into the NAcc reduced METH-primed reinstatement, but not when the V1AR was blocked. Our results demonstrate a substantial role for the V1AR in mediating the inhibitory effects of oxytocin on METH-primed reinstatement, and indicate the need for investigations into the differential involvement of V1ARs and OTRs in oxytocin-induced reduction of METH-related behaviours.
Location: United States of America
No related grants have been discovered for Sarah Baracz.