There have also been case reports of adolescents stealing OxyContin from their parents (Katz and Hays 2004). Effect of the administration of oxytocin as a therapeutic target in the addictive process induced by social stress in animal models alcohol brain fog and clinical studies. Prolonged exposure to social stress produces a desensitization of GC receptors [74,109,110], thus reducing the effectiveness of GCs in inhibiting transcription factors (e.g., NF-kB) and the intrinsic activity of HAT.
- Taken together, OXT treatment may be a useful therapeutic to reduce stress-related physiological responses (e.g. anxiety, craving) relevant to drug and alcohol use and relapse, though future studies are necessary in alcohol and drug dependent populations.
- The administration of OXT into the NAc decreased the cued reinstatement of cocaine self-administration [30].
- Pharmacies in some areas had stopped carrying OxyContin due to the fear of robberies (Suleman 2002).
- In support of this finding, central OXT administration did not prevent the acquisition of morphine-conditioned place preference (CPP), and instead, increased the expression of CPP in rats (Moaddab et al., 2015).
- Being able to avoid the limitations set by the BBB through intranasal administration opens up new opportunities for pharmaceutical treatments of disease.
OXT produces mixed effects with regard to modulating craving of cannabis, which may be determined by the level of dependence; for instance, it was shown to decrease craving induced by social stress in dependent individuals [55], while no effects were observed in recreational users [56]. There is huge scientific interest in the neuropeptide oxytocin (OXT) due to its putative capacity to modulate a wide spectrum of physiological and behavioral effects. It is mainly synthetized in the supraoptic nucleus (SON) and the paraventricular nucleus (PVN) of the hypothalamus, and the majority is released into the peripheral bloodstream through neurohypophysis [1]. In the periphery, OXT acts as a hormone that modulates parturition, lactation, and sexual stimulation, among other functions [2]. Little is known about the stability of the intranasal administration of oxytocin which was the administration route in the only human study seen thus far.
Distinct acute effects of LSD, MDMA, and d-amphetamine in healthy subjects
Further, IN OXT treatment decreased alcohol withdrawal symptoms in treatment-seeking patients compared to placebo and significantly reduced anxiety in dependent subjects following cessation of drinking (Pedersen, 2017, Pedersen et al., 2013). Taken together, OXT treatment may be a useful therapeutic to reduce stress-related physiological responses (e.g. anxiety, craving) relevant to drug and alcohol use and relapse, though future studies are necessary in alcohol and drug dependent populations. Other groups have evaluated the protective role of OXT against relapses into the consumption of different drugs of abuse as a result of social stress. OXT (1 mg/kg) attenuated alcohol-seeking behavior in a dose-related manner in male and female mice in response to an acute challenge with a predatory odor [176]. Similar results have been observed in the tempering of drug seeking and reinstatement due to different types of stress. Furthermore, systemic administration of OXT (1 mg/kg) decreased methamphetamine-seeking behavior after exposure to a predator’s odor [177] and administration of yohimbine in rats [50].
Choice between food and heroin
After repeated exposure to SD, the extra-hypothalamic release of CRF activates the mesocorticolimbic DA system [99]. This activation of the dopaminergic system produces a decrease in social interaction in animals as well as depressive-like symptoms and anhedonia, amongst other effects [100,101]. The serotonin and norepinephrine systems constitute other signaling systems involved in a series of mental disorders (anxiety, depression, etc.) and are also affected by social stress [102,103,104,105].
The discovery and development of new drugs that selectively target the OXTR will be key for future studies on the clinical utility of this therapeutic strategy for alcohol/drug addiction treatment. If favorable social housing can avoid the increase in the rewarding effects of cocaine induced by SD through an increment of OXT, we predicted that the same results could be obtained if we administered exogenous OXT to animals housed under standard conditions. sober living recovery homes To test this hypothesis, we administered, peripherally, one dose of OXT (1 mg/kg) before each agonistic encounter. In relation to cocaine, our results showed that the administration of OXT before each SD blocked the long-term increase in the conditioned rewarding effects of cocaine and cocaine SA induced by SD. We also observed that OXT was capable of undermining the reinstatement of cocaine-seeking behavior in the latter paradigm.
One possible hypothesis is that the local concentration reached by OXT may engage different signaling pathways to allow for more finely tuned signaling mechanisms and behavioral responses (Grinevich et al., 2016). Further, due to high structural homology OXT can also bind to and activate the related vasopressin receptor subtypes (V1a, V1b and V2) (Knobloch and Grinevich, 2014). Under some conditions, this may constitute alternative targets for OXT, especially at pharmacological concentrations and in brain regions that have little or no OXTR expression (Grinevich et al., 2016). Currently, there has been only one OXT receptor identified (Gimpl and Fahrenholz, 2001), and it is located in abundance throughout both central and peripheral systems. The OXT receptor (OXTR) is a member of the family of the rhodopsin-type 1 G protein-coupled receptor (GPCR) family and, together with three vasopressin receptor subtypes (V1a, V1b and V2), forms a subfamily of structurally related receptors (Devost et al., 2008).
3. Role of Oxytocin in Social Stress
Women who used hormonal contraceptives were tested regardless of menstrual cycle phase, but women not using hormonal contraceptives were tested only during the follicular phase (days 2–14; White et al, 2002). The study was approved by the Institutional Review Board at the University of Chicago in accordance with the Code of Federal Regulations (Title 45, Part 46) adopted by the National Institutes of Health and the Office for Protection from Research Risks of the US Federal Government. Participants provided written informed consent before participation and after completing all sessions they were debriefed to explain the study.
Interestingly, ample evidence has shown that both, OT and AVP are able to decrease the consumption of different drugs of abuse, as well as to ameliorate their rewarding and reinforcing effects. In particular, OT has been shown to be able to shift drug-induced reward into social-induced reward, mainly due to its interaction with the dopaminergic system. This phenomenon is also reflected in the results of clinical trials where intranasal OT shows promising efficacy in managing substance use disorder. Therefore, the aim of this review is to comprehensively characterize the involvement of OT and AVP in the rewarding and other behavioral effects of drugs of abuse in animal models, with a particular highlight on the impact of social factors on the observed effects. Understanding this relationship may contribute to higher drug development success rates, as a result of a more profound and deliberate studies design.
RxPATROL is a collaborative initiative between industry, different pharmacy organizations, and law enforcement to gather, assemble, analyze, and disseminate pharmacy theft intelligence to law enforcement throughout the nation. Purdue Pharma directed its sales representatives to begin using 11 indicators to identify possible abuse and diversion and to report the incidents to Purdue Pharma’s General Counsel’s Office for investigation. As of September 2003, through its own investigations, Purdue Pharma had identified 39 physicians and other healthcare professionals whom they referred to legal, medical, or regulatory authorities for further action (US General Accounting Office 2003). Purdue Pharma has also disseminated pain-related information to consumers through websites, and it also sponsors painfullyobvious.com, which discusses the dangers of abusing prescription drugs. Methamphetamine is proposed to upregulate inflammatory processes, in part, by activating toll-like receptor 4 (TLR4) [29].
Other Literature Sources
A transcardial perfusion was then performed (300 ml Dulbecco’s Modified Eagle Medium (Sigma-Aldrich) followed by 300 ml fresh ice cold 4% paraformaldehyde, at 16 ml/min). Brains were post-fixed in 4% paraformaldehyde for 24 h at 4 °C, and then placed in a cryoprotectant solution (20% sucrose, 30% ethylene glycol, how long can alcohol be detected 2% polyvinylpyrrolidone dissolved in 0.1 mol PBS) for storage at −20 °C until slicing. Vehicle (saline) or oxytocin (1 mg/kg) daily from PND 28–42 (early to mid-adolescence in rats [19]). There is one OT receptor, cloned in
1992(9), and it belongs to the
rhodopsin-type (class1) G protein-coupled receptor family.
Additionally, physical and social stress has been demonstrated to prime the immune system into a pro-inflammatory state, which in turn has been shown to modulate vulnerability to develop several health problems including drug addiction [58]. OXT has anti-stress and anti-inflammatory effects, and also enhances the stress-buffering effects of other interventions such as social support [59,60,61]. This effect can be explained broadly due to its potential to decrease the reactivity of the HPA axis by reducing the release of adrenocorticotropic hormone (ACTH) and corticotropin-releasing factor (CRF) [1].
During the acquisition phase, higher dose oxytocin significantly reduced the subjects’ time spent in the methamphetamine paired chamber relative to the group dosed without oxytocin or with lower doses [57]. However, during the conditioned place preference following the conditioning phase, oxytocin demonstrated no significant effect on conditioned place preference expression following methamphetamine exposure, suggesting oxytocin played no role in the prevention of learned drug-seeking behavior [57]. The results showed that the oxytocin group demonstrated a faster time to extinction than the methamphetamine group, though there was no significant dose-dependent relationship [57].
These OXT-treated animals displayed neuroinflammatory levels of chemokines (CX3CL1 and CXCL12) that were lower than those observed in non-treated defeated mice [61]. For example, intracerebroventricular administration of OXT (1 μg/µL) in adult male mice subjected to maternal separation mitigated the increase in the expression of genes relevant to the neuroinflammatory response (IL-1β, Myd88, TNF-α, TLR4, and Nlrp3) [190]. Moreover, intranasal administration of OXT (1 μg/µL) to male rats reversed the increase in IL-1β and IFN-γ levels in the mPFC and hippocampus induced by a rodent model of posttraumatic stress disorder [191].
The use of opioids in pain management has always been an area of debate and of course a lot of concern. The problem lies not only in the specific medication, but in the increasing base rate of addiction in the US and various means of availability of this medication (Passik 2001). The warning on OxyContin’s label may have been misleading and inadvertently provoked the nonmedical usage of the drug. To purport their addiction, abusers of OxyContin found out ways to compromise its time-release and certainly different ways to obtain it. This property could have provoked abusers to inject a solution of crushed OxyContin tablets to obtain a quick high.
Stress-induced reinstatement was inhibited by OT injected into the mPFC and reversed with an OT receptor antagonist. It was also inhibited when injected into the dorsal HPC, albeit at a higher dose and this effect was not reversed by an OT receptor antagonist. In summary, there is evidence that OT inhibits tolerance to opiates, and reduces opiate self-administration, and stress-induced reinstatement of extinguished opiate-taking behaviors.