EFFECTS OF CHRONIC ADMINISTRATION OF 7-BENZYLIDENE-7-DEHYDRONALTREXONE AND NALTRIBEN ON THE ANTINOCICEPTIVE ACTIONS OF DELTA(1)-OPIOID AND DELTA(2)-OPIOID RECEPTOR AGONISTS
Hn. Bhargava et al., EFFECTS OF CHRONIC ADMINISTRATION OF 7-BENZYLIDENE-7-DEHYDRONALTREXONE AND NALTRIBEN ON THE ANTINOCICEPTIVE ACTIONS OF DELTA(1)-OPIOID AND DELTA(2)-OPIOID RECEPTOR AGONISTS, European journal of pharmacology, 311(2-3), 1996, pp. 127-132
The effects of chronic administration of 7-benzylidene-7-dehydronaltre
xone, a delta(1)-opioid receptor antagonist acid naltriben, a delta(2)
-opioid receptor antagonist, on the antinociceptive responses to [D-Pe
n(2), D-Pen(5)]enkephalin and [D-Ala(2), Glu(4)]deltorphin II, delta(1
)- and delta(2)-opioid receptor agonists, respectively, were determine
d in the mouse. Female B6C3F1 mice were given 7-benzylidene-7-dehydron
altrexone (3 mg/kg/day), naltriben (1 mg/kg/day) or the vehicle by sub
cutaneously implanted Alzet osmotic minipumps for 7 days. Both [D-Pen(
2), D-Pen(5)]enkephalin and [D-Ala(2), Glu(4)]deltorphin II administer
ed intracerebroventricularly (i.c.v.) produced antinociceptive as meas
ured by the tail-flick test with ED(50) values of 6.76 and 6.68 mu g/m
ouse, respectively. Chronic administration of 7-benzylidene-7-dehydron
altrexone lowered the ED(50) of [D-Pen(2), D-Pen(5)]enkephalin but not
of [D-Ala(2), Glu(4)]deltorphin II. Chronic administration of naltrib
en lowered the ED(50) of [D-Ala(2), Glu(4)]deltorphin II but had no ef
fect on the ED(50) of [D-Pen(2), D-Pen(5)]enkephalin. The binding of [
H-3][D-Pen(2), D-Pen(5)]enkephalin to whole brain membranes of chronic
7-benzylidene-7-dehydronaltrexone-treated mice did not differ from ch
ronic vehicle-treated mice. On the other hand, chronic administration
of naltriben resulted in slight but reproducible elevation in the B-ma
x value of [H-3][D-Pen(2), D-Pen(5)]enkephalin to bind to whole brain
membranes in comparison to vehicle-injected controls. The results sugg
est that chronic treatment with delta(1)- and delta(2)-opioid receptor
antagonist cause behavioral supersensitivity to their agonists, respe
ctively, and provides further evidence for the existence of delta-opio
id receptor subtypes.