Contribution of the region anterior and ventral to the third ventricle to opiate withdrawal excitation of oxytocin secretion.
Virgin female or lactating rats were given infusion into a lateral cerebral ventricle (i.c.v.) of either morphine to produce tolerance and dependence or vehicle from a subcutaneous osmotic minipump for 5 days, then they were anaesthetized with urethane. In virgins either an electrolytic or sham lesion of the region anterior and ventral to the third ventricle (AV3V region) was made. Initial blood plasma concentrations of oxytocin, measured by radioimmunoassay were similar in i.c.v. morphine- and i.c.v. vehicle-infused rats (20.6 +/- 2.7 and 19.0 +/- 4.3 pg/ml, respectively). Naloxone (5 mg/kg i.v.) significantly increased oxytocin secretion in all groups for at least 60 min; oxytocin concentration at 6 min after naloxone was in the order: sham-lesioned i.c.v. morphine group (mean 1,839 +/- 809 pg/ml, n = 6), greater than AV3V-lesioned i.c.v. morphine group (326 +/- 65 pg/ml, n = 6), = sham-lesioned i.c.v. vehicle group (251 +/- 66 pg/ml, n = 6), greater than AV3V-lesioned i.c.v. vehicle group (47.2 +/- 12.4 pg/ml, n = 6). Thus in both intact and lesioned rats naloxone increased oxytocin secretion much more in morphine-dependent rats than in the respective controls; in both morphine-naive and morphine-dependent rats, the AV3V lesion reduced the effect of naloxone with respect to plasma oxytocin concentration, but not with respect to the increase relative to the lower prenaloxone concentrations in the lesioned rats (prenaloxone values in the lesioned rats were: i.c.v. vehicle group, 15.8 +/- 6.8 pg/ml; i.c.v. morphine group, 24.3 +/- 7.8 pg/ml; and in the sham-lesioned rats: i.c.v. vehicle group, 67.3 +/- 31.2 pg/ml, i.c.v. morphine group, 65.5 +/- 15.0 pg/ml). Thus the AV3V region is not essential for withdrawal excitation of oxytocin secretion in morphine-dependent rats. In lactating morphine-dependent rats, i.c.v. infusion of the angiotension II antagonist saralasin (2.5 micrograms/min) decreased plasma oxytocin concentration after 10 min (5.7 +/- 1.1 pg/ml, n = 7 vs. 13.2 +/- 3.2 pg/ml, n = 8), but did not prevent naloxone-provoked excitation of oxytocin secretion, measured by radioimmunoassay (6 min after naloxone in the i.c.v. saralasin group 402.8 +/- 124.5 pg/ml, n = 7 vs, in controls, 1,009 +/- 382 pg/ml, n = 7) or assessed by continuous recording of intramammary pressure. These results indicate that centrally acting angiotensin II is not an important mediator of naloxone-induced oxytocin hypersecretion in morphine-dependent rats.(ABSTRACT TRUNCATED AT 400 WORDS)
Russell
J A
JA
Department of Physiology, University Medical School, Edinburgh, UK.
Pumford
K M
KM
Bicknell
R J
RJ
D000804:Angiotensin II / Q000037:antagonists & inhibitors; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002552:Cerebral Ventricles / Q000503:physiopathology*; D005260:Female; D007263:Infusions, Parenteral; D007774:Lactation / Q000502:physiology; D009020:Morphine / Q000009:adverse effects*; D009270:Naloxone / Q000494:pharmacology*; D010121:Oxytocin / Q000097:blood / Q000378:metabolism*; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D012504:Saralasin / Q000008:administration & dosage; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*
D000804:Angiotensin II; D009270:Naloxone; D010121:Oxytocin; D009020:Morphine; D012504:Saralasin