Congenital vasopressin deficiency and acute and chronic opiate effects on hypothalamo-pituitary-adrenal axis activity in Brattleboro rats.
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.
Domokos
Agnes
A
Institute of Experimental Medicine, Hungarian Academy of Sciences, Szigony 43, 1083 Budapest, Hungary.
Mergl
Zsuzsa
Z
Barna
István
I
Makara
Gábor B
GB
Zelena
Dóra
D
D000311:Adrenal Glands / Q000187:drug effects* / Q000502:physiology; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D001127:Arginine Vasopressin / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000235:genetics; D007031:Hypothalamus / Q000187:drug effects* / Q000502:physiology; D017403:In Situ Hybridization; D008297:Male; D009020:Morphine / Q000008:administration & dosage*; D009154:Mutation; D010902:Pituitary Gland / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology; D011333:Pro-Opiomelanocortin / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011910:Rats, Brattleboro
D012333:RNA, Messenger; D001127:Arginine Vasopressin; D011333:Pro-Opiomelanocortin; D009020:Morphine; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone