Effects of nonapeptide antagonists on oxytocin- and arginine-vasopressin-induced analgesia in mice.
Several peptides, including arginine-vasopressin (AVP), neurotensin, and substance P, produce analgesia that is not mediated by opiate systems. Using the hot plate test, we studied the analgesic effects of intracisternal (i.c.) administration of various doses of the nonapeptide oxytocin (OXY) in Swiss-Webster mice. We found that OXY (1-4 micrograms) significantly increased the latency of animals to jump or lick their paws after placement on a hot plate. This effect was not blocked by naloxone pretreatment, which suggests that it is not opiate dependent. Using the hot plate test, we confirmed that AVP (1 and 4 micrograms) also produces analgesia. We then studied the analgesia produced by OXY and by AVP using 3 nonapeptide analogues with antagonist properties: [Pen1, LpMePhe2, Thr4, Orn8]OXY (PLMPTO-OXY) that has anti-oxytocic properties in the uterine contraction assay, d(CH2)5Tyr(Me)AVP(dTM-AVP) which antagonizes the antidiuretic properties of AVP and d(CH2)5D-Ile2,Abu4-AVP (dIA-AVP) which antagonizes the vasopressor effects of AVP. Simultaneous administration of PLMPTO-OXY completely blocked the analgesia produced by OXY whereas the antidiuretic antagonist dIA-AVP partially blocked OXY-induced analgesia and dTM-AVP had no effect. None of the antagonists used blocked AVP-induced analgesia. We concluded that the neural systems mediating the analgesic effects of i.c. OXY differ from those for AVP.
Caldwell
J D
JD
Department of Psychiatry, School of Medicine, University of North Carolina, Chapel Hill 27514.
Mason
G A
GA
Stanley
D A
DA
Jerdack
G
G
Hruby
V J
VJ
Hill
P
P
Prange
A J
AJ
Pedersen
C A
CA
D000698:Analgesia; D000818:Animals; D001127:Arginine Vasopressin / Q000037:antagonists & inhibitors*; D008297:Male; D051379:Mice; D009842:Oligopeptides / Q000494:pharmacology*; D010121:Oxytocin / Q000037:antagonists & inhibitors*
D009842:Oligopeptides; D001127:Arginine Vasopressin; D010121:Oxytocin