Persistent effects of the orexin-1 receptor antagonist SB-334867 on naloxone precipitated morphine withdrawal symptoms and nociceptive behaviors in morphine dependent rats
“…In a study conducted at our lab 32 , inhibition of OXR1 significantly reduced the development of morphine dependence and behavioral signs elicited by naloxone via diminution of cAMP response element-binding protein and phospholipase Cβ3 33 . Reduction of phospholipase Cβ3 may mediate impairment of memory development during a prolonged blockade of orexin 1 receptors 34 .…”
Objective Orexin neuropeptides are implicated in physical dependence on
opioids and expression of withdrawal symptoms in drug abuse. The paraventricular
nucleus of the midline thalamus (PVT) has a high expression of orexin receptors.
The current research studied the effect of orexin-A in the PVT area on the
development of behavioral indices produced by morphine withdrawal in rats.
Methods Male Wistar rats weighing 250–300 gr were utilised. To
produce drug dependence, morphine (6, 16, 26, 36, 46, 56, and
66 mg/kg, 2 ml/kg) was injected at an interval
of 24 hrs for 7 days. To assess the involvement of the orexin in withdrawal
syndrome, we injected orexin-A (100 μM, 200 nl) into the
PVT for 7 days before each morphine injection. On the day after the last
injection of morphine, naloxone (2.5 mg/kg, i.p.) was injected
to elicit the morphine withdrawal symptoms which were observed and checked for
25 min.
Results The results of the current research showed that the orexin-A in
PVT enhances the severity of behavioral symptoms prompted by the injection of
naloxone in drug-dependent rats.
Conclusions These observations imply that targeting the orexin receptors
in PVT might exhibit a new therapeutic strategy for the future treatment of
dependence.
“…In a study conducted at our lab 32 , inhibition of OXR1 significantly reduced the development of morphine dependence and behavioral signs elicited by naloxone via diminution of cAMP response element-binding protein and phospholipase Cβ3 33 . Reduction of phospholipase Cβ3 may mediate impairment of memory development during a prolonged blockade of orexin 1 receptors 34 .…”
Objective Orexin neuropeptides are implicated in physical dependence on
opioids and expression of withdrawal symptoms in drug abuse. The paraventricular
nucleus of the midline thalamus (PVT) has a high expression of orexin receptors.
The current research studied the effect of orexin-A in the PVT area on the
development of behavioral indices produced by morphine withdrawal in rats.
Methods Male Wistar rats weighing 250–300 gr were utilised. To
produce drug dependence, morphine (6, 16, 26, 36, 46, 56, and
66 mg/kg, 2 ml/kg) was injected at an interval
of 24 hrs for 7 days. To assess the involvement of the orexin in withdrawal
syndrome, we injected orexin-A (100 μM, 200 nl) into the
PVT for 7 days before each morphine injection. On the day after the last
injection of morphine, naloxone (2.5 mg/kg, i.p.) was injected
to elicit the morphine withdrawal symptoms which were observed and checked for
25 min.
Results The results of the current research showed that the orexin-A in
PVT enhances the severity of behavioral symptoms prompted by the injection of
naloxone in drug-dependent rats.
Conclusions These observations imply that targeting the orexin receptors
in PVT might exhibit a new therapeutic strategy for the future treatment of
dependence.
“…In addition to choosing the objective indicator of weight loss, agitation is a specific indicator of the rat’s withdrawal response, so the modified Yanagi Koji score standard was also selected for comprehensive score comparison. 29 , 30 …”
Section: Discussionmentioning
confidence: 99%
“…Rats in the control group were injected with normal saline. 29 , 30 Figure 2 The morphine-dependent rat model (Naloxone-precipitated withdrawal) and treatment of OA. …”
Section: Methodsmentioning
confidence: 99%
“…The morphine-dependent rat model was replicated from previous studies using the dose-escalation method. 27,28 Seventy rats were randomly divided into 7 groups (I-VII) as shown in Figure 1. Group I was a normal control group where normal saline was injected subcutaneously (s.c.).…”
Section: The Morphine-dependent Rat Model (Spontaneous Withdrawal)mentioning
Introduction: Oleanolic acid (OA) has been shown to be useful for the treatment of mental disorders. Methods: In this study, we investigated the effects of OA in animal models of spontaneous withdrawal and naloxone-precipitated withdrawal and evaluated the effects of OA on the acquisition, extinction, and reinstatement of morphine-induced conditioned place preference (CPP). Results: OA significantly improved symptoms of withdrawal, and significantly reduced the acquisition and reinstatement of morphine-induced conditioned place preference. Moreover, OA significantly reduced the serum content of 5-hydroxy tryptamine (5-HT) and dopamine (DA) in a dose-dependent manner, and reduced norepinephrine (NE) and 5-HT content in the frontal cortex (PFC), while significantly increasing endorphin content in rats. OA also significantly reduced serum DA content in mice.
Conclusion:These results indicate that OA can improve the withdrawal symptoms of rats and mice by regulating the DA system and suggest that OA may be useful in treatment of morphine addiction.
“…Inhibition of OXR1 with SB-334867 induced a significant alleviation of the development of morphine dependence and behavioral symptoms induced by naloxone administration in rats. In addition, long-term blockade of OXR1 may reduce formalininduced nociception (63).…”
Section: Icv Intrcerebroventricularis; Lc Locus Coeruleus; Lpgi Parag...mentioning
Physical disability constitutes a large proportion of the population both in the world and in Turkey. However, the problems related to marriage life, sexuality and sexual life of this population have not been adequately studied. The aim of this study is to evaluate the effect of sexual myths on the sexual quality of life, marital satisfaction and self-esteem in married women with physical disability. This descriptive and cross-sectional study was conducted between May 2022 - March 2023. The data of the study were collected by face-to-face interviews with physically disabled married women registered with the Disabled Associations in Zonguldak. The study was completed with 266 physically disabled married women who met the inclusion criteria. “Personal Charateristics Form”, “Sexual Myths Scale”, “Sexual Quality of Life Scale-Female”, “Marital Satisfaction Scale” and “Rosenberg Self-Esteem Scale” were used for the data collection. SPSS was used to analyze the data. In the study, the level of belief in sexual myths of disabled married women was found to be above the medium level, and their sexual life quality, marital satisfaction and self-esteem were found to be low level. In addition, It was determined that there was a negative and strong relationship between belief in sexual myths and quality of sexual life (r=-0.71; p<0.001); there was a negative and moderate relationship between belief in sexual myths and marital satisfaction (r=-0.51; p<0.05) and self-esteem (r=-0.58; p<0.05). This study showed that married women with disability experience problems in their sexual lives. It is thought that the data obtained from the study will contribute to the literature.
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