Naloxone Antagonism of Corticotropin-Releasing Hormone Stimulation of Prolactin Secretion in Rhesus Monkeys*

VanVugt, Dean A.; Webb, Michelle Y.; Reid, Robert L.

doi:10.1210/jcem-68-6-1060

Cited by 16 publications

(4 citation statements)

References 32 publications

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“…Other than one human study reporting an increase in serum prolactin following intramuscular administration of naloxone 210 mg (Kumor et al, 1988), extensive studies in non-human primates and humans have not found an effect of this mu-opioid receptor antagonist on serum prolactin (Volavka et al, 1980;Morley et al, 1980;Naber et al, 1981;Cohen et al, 1983Cohen et al, , 1985van Bergeijk et al, 1986;VanVugt et al, 1989b). Data for naltrexone and nalmefene, the two antagonists with greater affinity at mu-and kappa-opioid receptors than naloxone, are, however, mixed.…”

Section: Prolactin and Mu-and Kappa-opioidergic Drugsmentioning

confidence: 99%

“…One nonhuman primate study found that nalmefene suppressed basal prolactin, whereas its quaternary ammonium form, which does not penetrate the blood-brain barrier, had no effect on prolactin (Simpkins et al, 1991). Another study found that nalmefene had no effect on serum prolactin in male rhesus monkeys (Mello et al, 2000), while another group found that nalmefene stimulated prolactin release in normal female rhesus monkeys but not in ovariectomized monkeys (VanVugt et al, 1989b). Naltrexone 50 mg stimulated prolactin release in normal male volunteers, early follicular phase female volunteers, and, following daily dosing for 1 week, in luteal phase female volunteers (Volavka et al, 1979;Mendelson et al, 1986;Gindoff et al, 1988), although, when studied in males, naltrexone 100 mg had no effect on prolactin (Volavka et al, 1979).…”

Section: Prolactin and Mu-and Kappa-opioidergic Drugsmentioning

confidence: 99%

“…Human studies have shown that the mu-opioid receptor agonist methadone and the kappa-opioid receptor agonist dynorphin A(1-13) each stimulate prolactin release; and non-human primate and human studies have shown that the increase in serum prolactin following acute administration of mu-and kappaopioid agonists is blocked by administration of an opioid antagonist (Kreek, 1978;Wehrenberg et al, 1981;Pfeiffer et al, 1986;VanVugt et al, 1989a;Ur et al, 1997;Kreek et al, 1999). While mu-and kappa-opioid antagonists have generally been shown to have no effect on serum prolactin, there are conflicting data in females indicating that prolactin response to these antagonists may be affected by menstrual cycle phase (Ellingboe et al, 1980;Mendelson et al, 1986;VanVugt et al, 1989b;Butelman et al, 1999;Mello et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

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Nalmefene Induced Elevation in Serum Prolactin in Normal Human Volunteers: Partial Kappa Opioid Agonist Activity?

Bart

Schluger

Borg

et al. 2005

Neuropsychopharmacol

126

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In humans, mu-and kappa-opioid receptor agonists lower tuberoinfundibular dopamine, which tonically inhibits prolactin release. Serum prolactin is, therefore, a useful biomarker for tuberoinfundibular dopamine. The current study evaluated the unexpected finding that the relative mu-and kappa-opioid receptor selective antagonist nalmefene increases serum prolactin, indicating possible kappa-opioid receptor agonist activity. In all, 33 healthy human volunteers (14 female) with no history of psychiatric or substance use disorders received placebo, nalmefene 3 mg, and nalmefene 10 mg in a double-blind manner. Drugs were administered between 0900 and 1000 on separate days via 2-min intravenous infusion. Serial blood specimens were analyzed for serum levels of prolactin. Additional in vitro studies of nalmefene binding to cloned human kappa-opioid receptors transfected into Chinese hamster ovary cells were performed. Compared to placebo, both doses of nalmefene caused significant elevations in serum prolactin (po0.002 for nalmefene 3 mg and po0.0005 for nalmefene 10 mg). There was no difference in prolactin response between the 3 and 10 mg doses. Binding assays confirmed nalmefene's affinity at kappa-opioid receptors and antagonism of mu-opioid receptors. [ 35 S]GTPgS binding studies demonstrated that nalmefene is a full antagonist at mu-opioid receptors and has partial agonist properties at kappa-opioid receptors. Elevations in serum prolactin following nalmefene are consistent with this partial agonist effect at kappa-opioid receptors. As kappaopioid receptor activation can lower dopamine in brain regions important to the persistence of alcohol and cocaine dependence, the partial kappa agonist effect of nalmefene may enhance its therapeutic efficacy in selected addictive diseases.

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Section: Prolactin and Mu-and Kappa-opioidergic Drugsmentioning

confidence: 99%

Section: Prolactin and Mu-and Kappa-opioidergic Drugsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Nalmefene Induced Elevation in Serum Prolactin in Normal Human Volunteers: Partial Kappa Opioid Agonist Activity?

Bart

Schluger

Borg

et al. 2005

Neuropsychopharmacol

126

View full text Add to dashboard Cite

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“…Several explanations may account for this discrepancy: exogenous opiates may show pharmacological and not physiological effects; and apparently, some opiates have agonist activity, as well as antagonist activity (13). Furthermore, opiates differ in their relative affinity for different receptor subtypes (13,32), and the in vivo function of endogenous opioids may involve receptors that are relatively insensitive to naloxone (3,9,13,(33)(34)(35). Naloxone is a competitive inhibitor of opiate receptors; but in low doses, it has the highest affinity for -and ⑀-receptors, whereas relatively large doses are required to block the ␦-and -receptors (3,33).…”

Section: Discussionmentioning

confidence: 99%

The Effects of Endogenous Opioids and Cortisol on Thyrotropin and Prolactin Secretion in Patients with Addison’s Disease¹

Hangaard¹,

Andersen²,

Grodum³

et al. 1999

The Journal of Clinical Endocrinology & Metabolism

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This study assessed the controversial role of endogenous opioids and cortisol in the regulation of TSH and PRL secretion in humans. Seven euthyroid male patients with Addison's disease were studied four times, with an interval of 1-3 months, as follows: 1) during normocortisolism [graduated infusion of hydrocortisone, 0.4 mg/kg, over 19.5 h]; 2) normocortisolism and coadministration of naloxone, at 25 g/kg⅐h during the last 6.5 h; 3) hypocortisolism (24 h withdrawal of hydrocortisone, followed by 19.5 h saline infusion); and 4) hypocortisolism plus naloxone administration. The TSH and PRL levels were measured every 15 min, from 0800 -1530 h. A TRH test was performed at 1300 h and 1400 h (10 g and 200 g of TRH, respectively). The mean TSH level increased significantly during hypocortisolism, compared with normocortisolism (1.78 Ϯ 0.04 vs. 0.84 Ϯ 0.02 mU/L; P Ͻ 0.001). The administration of naloxone suppressed the TSH levels during hypo-and normocortisolism (1.78 Ϯ 0.04 vs. 1.50 Ϯ 0.03 and 0.84 Ϯ 0.02 vs. 0.61 Ϯ 0.02 mU/L, respectively; P Ͻ 0.001). During hypocortisolism, the TSH responses to small and high doses of TRH were significantly higher than during normocortisolism (P Ͻ 0.02). Naloxone had no effect on the TSH responses to TRH, neither during hypo-nor during normocortisolism. The mean PRL level increased significantly during hypocortisolism, compared with normocortisolism (5.8 Ϯ 0.4 vs. 3.6 Ϯ 0.2 g/L; P Ͻ 0.001), and naloxone induced an increase in PRL levels both during hypo-and normocortisolism (7.1 Ϯ 0.7 vs. 4.7 Ϯ 0.5 g/L, respectively; P Ͻ 0.01). The PRL responses to TRH were similar during hypo-and normocortisolism and without any change during opioid receptor blockade. In conclusion, cortisol suppressed basal TSH and PRL secretion and reduced the sensitivity of the thyrotrophs to TRH, without affecting the PRL response to TRH. Our results suggest that endogenous opioids act at the hypothalamic level to stimulate TSH secretion and to suppress the PRL secretion, but these results argue against an essential role of endogenous opioids in the physiological regulation of TSH and PRL secretion in humans. (J Clin Endocrinol Metab 84: 1595-1601, 1999 T HE ENDOCRINE mechanisms subserving an increased TSH and PRL secretion during acute stress (1) and suppressed TSH and PRL levels during more prolonged stress situations are not fully understood. The endogenous opioids have been clearly implicated in the control of secretion of gonadotropins, ACTH, and vasopressin (2-5); but their role, if any, in controlling TSH and PRL is disputable.In rats, opioid peptides have an inhibitory influence on TSH secretion, apparently mediated via a decreased TRH release from the hypothalamus (6), although an involvement of opioid receptors, both inside and outside the blood-brainbarrier, has been suggested (7). Human studies, evaluating the effect of exogenous opiates or the effect of the opioid receptor antagonist naloxone, have led to conflicting results, depending on the dose and duration of treatment used in different...

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Endocrine Effects of Opioid Antagonists

Mendelson

Mello

2009

Opiate Receptors and Antagonists

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Naloxone Antagonism of Corticotropin-Releasing Hormone Stimulation of Prolactin Secretion in Rhesus Monkeys*

Cited by 16 publications

References 32 publications

Nalmefene Induced Elevation in Serum Prolactin in Normal Human Volunteers: Partial Kappa Opioid Agonist Activity?

Nalmefene Induced Elevation in Serum Prolactin in Normal Human Volunteers: Partial Kappa Opioid Agonist Activity?

The Effects of Endogenous Opioids and Cortisol on Thyrotropin and Prolactin Secretion in Patients with Addison’s Disease¹

Endocrine Effects of Opioid Antagonists

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Naloxone Antagonism of Corticotropin-Releasing Hormone Stimulation of Prolactin Secretion in Rhesus Monkeys*

Cited by 16 publications

References 32 publications

Nalmefene Induced Elevation in Serum Prolactin in Normal Human Volunteers: Partial Kappa Opioid Agonist Activity?

Nalmefene Induced Elevation in Serum Prolactin in Normal Human Volunteers: Partial Kappa Opioid Agonist Activity?

The Effects of Endogenous Opioids and Cortisol on Thyrotropin and Prolactin Secretion in Patients with Addison’s Disease1

Endocrine Effects of Opioid Antagonists

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The Effects of Endogenous Opioids and Cortisol on Thyrotropin and Prolactin Secretion in Patients with Addison’s Disease¹