Interruption of parturition in rats by morphine: a result of inhibition of oxytocin secretion.
Oxytocin secretion is inhibited by opioids, and oxytocin is important in parturition. The effects on parturition of morphine, a relatively selective mu-opioid receptor agonist, were studied in the rat. Morphine or vehicle with or without the opiate antagonist naloxone were administered immediately after the birth of the second pup and the subsequent course of parturition was recorded in a total of 80 rats. Both s.c. morphine (10 mg/kg) and intracerebroventricular (i.c.v.) morphine (18 micrograms through a previously implanted cannula) interrupted parturition, delaying the birth of the sixth pup after treatment to 187.3 +/- 35.9 (S.E.M.) min and 195.4 +/- 19.5 min respectively, compared with 46.4 +/- 3.7 and 66.1 +/- 17.5 min after vehicle alone. The dose of morphine given i.c.v. had no effect when given s.c. Naloxone given concurrently prevented the effects of morphine. Eventually the rate of parturition in the morphine-treated groups recovered. Perinatal pup mortality rate was not increased when morphine was given to the mothers, but it did inhibit the expression of normal intrapartum maternal behaviour. Pup mortality was increased 48 h post partum by morphine given during parturition, and it reduced the proportion of rats with normal maternal behaviour 24 h post partum. Morphine did not affect spontaneous or oxytocin-stimulated contractile activity of the parturient uterus in vitro. The concentration of oxytocin in trunk blood plasma was decreased 40 min after i.c.v. morphine (24.3 +/- 3.9 vs 39.3 +/- 6.5 pmol/l in controls), as was vasopressin (7.2 +/- 1.5 vs 19.7 +/- 4.5 pmol/l in controls). Intravenous infusion of oxytocin (2-5 mU/min for 144.3 +/- 8.2 min; total infused 448.5 +/- 61.9 mU) after i.c.v. morphine re-started parturition; all pups were born to these rats (mean time to pup 6, 110.3 +/- 12.7 min) before the i.v. vehicle-infused rats given i.c.v. morphine re-started (mean time to pup 6, 406.3 +/- 125.2 min). It is concluded that morphine given during parturition acts centrally through opioid receptors to inhibit oxytocin secretion, and impairs the expression of maternal behaviour. Reversal of the effects of morphine on parturition by i.v. oxytocin demonstrates the important role of oxytocin in fetus ejection and expulsion.
Department of Physiology, University of Edinburgh Medical School.
J A
JA
Russell
R G
RG
Gosden
E M
EM
Humphreys
R
R
Cutting
N
N
Fitzsimons
V
V
Johnston
S
S
Liddle
S
S
Scott
J A
JA
Stirland
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D007276:Injections, Intraventricular; D007279:Injections, Subcutaneous; D007743:Labor, Obstetric / Q000187:drug effects*; D008425:Maternal Behavior; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D010121:Oxytocin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D014590:Uterine Contraction / Q000187:drug effects
D009270:Naloxone; D010121:Oxytocin; D009020:Morphine