Experiments were conducted to (1) provide further evidence of the selectivity of [D-Ala2,Leu5,Cys6]
enkephalin (
DALCE) as an antagonist of delta (
delta) receptor ligands and (2) use
DALCE as a tool to explore the possible role of
delta receptors in restraint stress. Dose- and time-response curves were generated for the respective delta- and mu (mu)-selective
opioid agonists
DPDPE (3-30 micrograms) and
DAGO (0.03-0.3 microgram) to increase the latency to paw-lick in the hot-plate test in rats. Both agonists produced robust
analgesia lasting at least 20 min when injected intracerebroventricularly (i.c.v.).
DALCE (0.4-10 micrograms) administered i.c.v. 24 h earlier failed to affect baseline
pain sensitivity.
DALCE pretreatment dose-dependently blocked the increase in paw-lick latency produced by
DPDPE (30 micrograms) but not that induced by an equivalent
analgesic dose of
DAGO (0.3 microgram). In the last experiment we determined whether 1 h of restraint stress would (a) alter
delta receptor sensitivity as indexed by
DPDPE-induced
analgesia and (b) attenuate the ability of
DALCE to functionally antagonize
DPDPE-induced
analgesia. Rats were assigned to one of four treatment groups: i.c.v. vehicle injection/no stress; vehicle/stress; i.c.v.
DALCE (10 micrograms)/no stress;
DALCE/stress. Twenty-four hours
after treatment, dose- and time-response curves were generated to test the ability of
DPDPE (30-120 micrograms) to increase paw-lick latency. Prior exposure to stress alone produced tolerance to
DPDPE-induced
analgesia.
DALCE pretreatment antagonized
DPDPE similarly regardless of stress condition. The effects of both stress and
DALCE were surmounted by the highest dose of
DPDPE.(ABSTRACT TRUNCATED AT 250 WORDS)