Stress Symptoms Induced by Repeated Morphine Withdrawal in Comparison to Other Chronic Stress Models in Mice

Zelena, Dóra; Barna, István; Mlynarik, Martin; Gupta, O. P.; Ježová, Daniela; Makara, Gábor B.

doi:10.1159/000087034

Cited by 30 publications

(20 citation statements)

References 86 publications

(56 reference statements)

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“…In agreement with previous studies, evaluation of serum corticosterone concentration showed an increase in corticosterone level following 4 hr morphine withdrawal in dependent animals [6,7].…”

Section: Discussionsupporting

confidence: 93%

“…Morphine withdrawal is associated with activation of the HPA [5]. A study has shown that repeated short periods of drug withdrawal (24 or 72 hr) in morphine-dependent mice represent a mild stress load [6] and animals undergoing acute (12 hr) morphine withdrawal displayed a potentiated and prolonged corticosterone response to restraint [7].Previous studies in both animal and human beings indicate that stress and glucocorticoids modulate various phases of memory processing [8][9][10]. Acute administration of glucocorticoid hormones enhances memory consolidation or acquisition in both animals and human beings in a dosedependent manner but usually impairs the retrieval of previously acquired information [11][12][13].…”

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Metyrapone and Mifepristone Reverse Recognition Memory Loss Induced by Spontaneous Morphine Withdrawal in Mice

Mesripour

Hajhashemi

Rabbani

2008

Basic Clin Pharma Tox

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Morphine withdrawal leads to an increase in corticosterone concentration in plasma, and cognitive deficits are found after withdrawal. Evidence indicates that glucocorticoid hormones affect memory. The aim of the current study was to evaluate the effects of metyrapone and mifepristone on memory deficit following spontaneous morphine withdrawal. Memory was tested by using the object recognition task. The novel object recognition task was carried out in a square wooden open-field apparatus using objects. The test was comprised of three sections: habituation for 15 min., first trial for 12 min. and test trial for 5 min. In this learning paradigm, the difference in exploration between a previously seen object and a novel object is taken as an index of memory performance (recognition index -RI). Male mice were made dependent by increasing doses of morphine (30 -90 mg/kg) subcutaneously twice daily for 3 days. RI was assessed 4 hr after the last dose of morphine on the third day. Mifepristone (50 and 100 mg/kg) and metyrapone (12.5 and 25 mg/kg) were used subcutaneously before the first trial and effects were compared to control values. Metyrapone (25 mg/kg) and mifepristone (50 mg/kg) improved RI to 34.8 ± 10.8% and 25.4 ± 11.7%, respectively, which are significantly different from control values (RI = − 14.8 ± 10.7%, P < 0.05). These results show that increased glucocorticoid concentration may be involved in memory deficit caused by morphine withdrawal. Metyrapone by inhibiting glucocorticoid formation, and mifepristone by inhibiting glucocorticoid receptors may be useful for preventing memory deficit following morphine withdrawal.Brain imaging studies involving human opiate addicts have indicated that many brain areas are hypofunctional during both prolonged abstinence [1] and acute withdrawal [2]. Chronic misuse of opiates will also lead to long-lasting impairments in brain function [3]. This event may relate to the cognitive deficits found, as well as to symptoms of anxiety and depression that linger after the physical symptoms of withdrawal have dissipated [4]. Such effects in human beings will require additional rehabilitation for cognitive deficits that impair everyday function, or else will cause drug-seeking urge. Therefore, looking for pharmacological trends that can prevent this cognitive impairment would be rational.Emotionally arousing experiences activate the hypothalamicpituitary-adrenocortical axis (HPA), resulting in elevated glucocorticoid levels (i.e. corticosterone and cortisol). Morphine withdrawal is associated with activation of the HPA [5]. A study has shown that repeated short periods of drug withdrawal (24 or 72 hr) in morphine-dependent mice represent a mild stress load [6] and animals undergoing acute (12 hr) morphine withdrawal displayed a potentiated and prolonged corticosterone response to restraint [7].Previous studies in both animal and human beings indicate that stress and glucocorticoids modulate various phases of memory processing [8][9][10]. Acute administration of gluco...

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Section: Discussionsupporting

confidence: 93%

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Metyrapone and Mifepristone Reverse Recognition Memory Loss Induced by Spontaneous Morphine Withdrawal in Mice

Mesripour

Hajhashemi

Rabbani

2008

Basic Clin Pharma Tox

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“…Chronic administration of morphine may result in tolerance to the stimulatory effect of the opioid on the HPA axis (Buckingham & Cooper 1984, Ignar & Kuhn 1990; the secretion of pituitary ACTH in response to (other) stressors may become suppressed (Briggs & Munsoon 1955, Buckingham & Cooper 1984. In contrast, chronic intermittent (e.g., twice daily) administration of morphine may lead to chronic stress probably as a consequence of repeated withdrawal (Houshyar et al 2001a, Zelena et al 2005.…”

Section: Introductionmentioning

confidence: 99%

Congenital vasopressin deficiency and acute and chronic opiate effects on hypothalamo-pituitary–adrenal axis activity in Brattleboro rats

Domokos¹,

Mergl²,

Barna³

et al. 2007

Journal of Endocrinology

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A growing body of evidence suggests that vasopressinergic activity in the hypothalamus is important in stress-related behaviors (like drug abuse) in line with a role in the regulation of the hypothalamo-pituitary-adrenal axis (HPA). We hypothesized that in the naturally vasopressin-deficient Brattleboro rat, acute and chronic morphine treatment may lead to reduced HPA axis activity. Rats were treated either with a single dose of morphine (10 mg/kg subcutaneously) and serial blood samples were taken or were treated twice daily with increasing doses of morphine (10-100 mg/kg subcutaneously) for 16 days and animals were killed by decapitation 4 or 16 h after the last injection. Single morphine injection induced a biphasic ACTH and corticosterone elevation with smaller increases in vasopressin-deficient rats. Chronic morphine treatment induced the typical somatic and HPA axis changes of chronic stress; the absence of vasopressin did not prevent these changes. In rats repeatedly treated with morphine plasma, ACTH and corticosterone levels were elevated both 4 and 16 h after the last injection (short and long withdrawal) and the absence of vasopressin attenuated this response. Our data suggest that vasopressin plays a prominent role in morphine treatment and withdrawalinduced acute hormonal changes, but does not affect development of chronic hyperactivity of the HPA axis.

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“…One of the most susceptible risk factors in this disease is any kind of emotional stress [4]. Opioid withdrawal can be an origin of stress for opioid addicted patients [9]. Therefore the stress that stem from opioid withdrawal may be an underlying cause of Graves' disease.…”

Section: Discussionmentioning

confidence: 99%

Abstaining Opioid Drugs as a Possible Risk Factor for Graves’ Disease

Boroujeni¹

2012

J Addict Res Ther

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Stress Symptoms Induced by Repeated Morphine Withdrawal in Comparison to Other Chronic Stress Models in Mice

Cited by 30 publications

References 86 publications

Metyrapone and Mifepristone Reverse Recognition Memory Loss Induced by Spontaneous Morphine Withdrawal in Mice

Metyrapone and Mifepristone Reverse Recognition Memory Loss Induced by Spontaneous Morphine Withdrawal in Mice

Congenital vasopressin deficiency and acute and chronic opiate effects on hypothalamo-pituitary–adrenal axis activity in Brattleboro rats

Abstaining Opioid Drugs as a Possible Risk Factor for Graves’ Disease

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