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

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Abstract

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 withdrawal-induced acute hormonal changes, but does not affect development of chronic hyperactivity of the HPA axis.

Original languageEnglish
Pages (from-to)113-121
Number of pages9
JournalJournal of Endocrinology
Volume196
Issue number1
DOIs
Publication statusPublished - Jan 2008

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Opiate Alkaloids
Brattleboro Rats
Neurogenic Diabetes Insipidus
Morphine
Vasopressins
Corticosterone
Adrenocorticotropic Hormone
Injections
Decapitation
Hypothalamus
Substance-Related Disorders
Therapeutics

ASJC Scopus subject areas

  • Endocrinology
  • Medicine(all)

Cite this

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abstract = "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 withdrawal-induced acute hormonal changes, but does not affect development of chronic hyperactivity of the HPA axis.",
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