Stimulation of the Hypothalamic-Pituitary-Adrenal Axis with the Opioid Antagonist Nalmefene

Geer, Eliza B.; Landman, Rita E.; Wardlaw, Sharon L.; Conwell, Irene M.; Freda, Pamela U.

doi:10.1007/s11102-005-5227-6

Cited by 13 publications

(8 citation statements)

References 46 publications

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“…Nalmefene injection produced a greater increase in ACTH and cortisol than naloxone, possibly indicating kappa-opioid receptor involvement in the regulation of the HPA axis (Schluger et al, 1998). A dose-dependent relationship and diurnal variation of ACTH and cortisol release involving an alpha-2 adrenergic mechanism (Geer et al, 2005) were also observed after naloxone administration (al-Damluji et al, 1990; Coiro et al, 1985; Delitala et al, 1994; Ehrenreich et al, 1987; Hernandez-Avila et al, 2003; Martin del Campo et al, 1994), but ACTH levels were not significantly elevated after naloxone infusion in 7 male high-dose methadone-maintained addicts. However, there was a significant and robust post-naloxone increase in ACTH levels in healthy controls (Gold et al, 1981).…”

Section: Discussionmentioning

confidence: 96%

Opioid and cocaine combined effect on cocaine-induced changes in HPA and HPG axes hormones in men

Goletiani

Mendelson

Sholar

et al. 2009

Pharmacology Biochemistry and Behavior

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Nalbuphine, a mixed mu-/kappa-opioid analgesic, may have potential as a new medication for the treatment of cocaine abuse. Kappa-opioid agonists functionally antagonize some abuse-related and locomotor effects of cocaine, and both kappa-selective and mixed mu-/kappa-opioids reduce cocaine self-administration by rhesus monkeys. Because cocaine's interactions with the hypothalamicpituitary-adrenal and (HPA) hypothalamic-pituitary-gonadal (HPG) axes may contribute to its reinforcing properties, we examined the effects of cocaine alone and in combination with nalbuphine. Neuroendocrine effects of a single dose of cocaine alone (0.2 mg/kg, IV), with nalbuphine (5 mg/70 kg, IV) + cocaine (0.2 mg/kg, IV) in combination were compared in seven adult men (ages 18-35) who met DSM-IV criteria for current cocaine abuse. Cocaine alone, and in combination with nalbuphine was administered on separate test days under placebo-controlled, double blind conditions. Cocaine stimulated ACTH, cortisol, and LH, whereas cocaine + nalbuphine in combination produced a smaller increase in ACTH, and decreased cortisol and LH. Thus it appears that nalbuphine attenuated cocaine's effects on ACTH, cortisol, and LH. These data are consistent with our earlier report that nalbuphine modestly attenuated cocaine's positive subjective effects, and that the subjective and cardiovascular effects of cocaine + nalbuphine in combination were not additive.

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Section: Discussionmentioning

confidence: 96%

Opioid and cocaine combined effect on cocaine-induced changes in HPA and HPG axes hormones in men

Goletiani

Mendelson

Sholar

et al. 2009

Pharmacology Biochemistry and Behavior

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“…The authors have suggested that perhaps subpopulations of patients under physiological or psychological stress may react to naltrexone with dysphoric symptoms. This has not been directly investigated, but there is evidence that the opioid system within areas of the limbic circuit could modulate the stress response in animals (i.e., opioids have been shown to reduce stress related neuroendocrine and autonomic responses) [84] and activate the hypothalamic–pituitary–adrenal (HPA) axis in humans [85,86].…”

Section: The Opioid System: μ‐Opioid Receptor Antagonistsmentioning

confidence: 99%

Neuropsychiatric Adverse Effects of Centrally Acting Antiobesity Drugs

Nathan

O’Neill

Napolitano

et al. 2011

CNS Neuroscience & Therapeutics

106

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“…This is also supported by the fact that naloxone treatment did not stimulate cortisol secretion after hypophyseal stalk transection in gilts ( Estienne et al, 1988 ). Nevertheless, naloxone has been shown to induce ACTH release in healthy human subjects ( Geer et al, 2005 ) and the effect seems to be gender specifi c Chong et al, 2006 ). In conclusion, it seems that the central nervous beta adrenergic and opioidergic systems regulate the cortisol response to stres-sors differently.…”

Section: Discussionmentioning

confidence: 89%

Beta-adrenergic and Opioidergic Modulation of Cortisol Secretion in Response to Acute Stress

Jb¹,

Parvizi²

2007

Exp Clin Endocrinol Diabetes

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The modulatory action of beta-adrenergic and opioidergic pathways on the cortisol response to acute stressors was investigated using gonadectomized male miniature pigs. Three types of stressors, nose-snare (NS, for 2 min. each on four occasions at 30 min. intervals); high intensity cracker blasts (CB, two blasts at 3 min intervals) and ACTH (1 i.u./kg BW, i.v.) were utilized 80 min after start of blood sampling. For assessment of cortisol blood samples were withdrawn every 20 min for 200 min. In addition, animals received i.v. injections of either isoproterenol (5 microg/ kg) or propranolol (0.5 mg/kg) or naloxone (1 mg/kg) 15 or 30 min before the application of stressor. Stress of repeated NS application as well as ACTH treatment, resulted in immediate secretion of cortisol (p<0.001). Blast of crackers resulted in a transient increase in cortisol (p<0.05). Isoproterenol stimulated the basal cortisol secretion for about 20 min in unstressed pigs (p <0.01) but propranolol had no effects. Isoproterenol also reinforced (p<0.05) the effect of CB, but had no effect on the cortisol response to nose-snare. In contrast, response to NS was reduced (p=0.02) by propranolol. Neither isoproterenol nor propranolol altered the cortisol response to ACTH application. Pretreatment with naloxone significantly increased the cortisol response to NS (p<0.01) and to CB (p<0.01), but had no effects on ACTH-induced cortisol release. In conclusion, the beta-adrenergic involvement is evident in the cortisol response to acute stress of nose-snare. Furthermore, the results indicate that activation of endogenous opioid system during stress mitigates adrenal response.

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Stimulation of the Hypothalamic-Pituitary-Adrenal Axis with the Opioid Antagonist Nalmefene

Cited by 13 publications

References 46 publications

Opioid and cocaine combined effect on cocaine-induced changes in HPA and HPG axes hormones in men

Opioid and cocaine combined effect on cocaine-induced changes in HPA and HPG axes hormones in men

Neuropsychiatric Adverse Effects of Centrally Acting Antiobesity Drugs

Beta-adrenergic and Opioidergic Modulation of Cortisol Secretion in Response to Acute Stress

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