The application of 80 footshocks (S-80) to mice induces a decrease in
nociceptive responses as measured by the tail-flick test, which is opi
oid mediated as well as prevented by naloxone (10 mg/kg, SC). When the
stress is prolonged up to 240 shocks (S-240) (i.e., from 6 min 40 s t
o 20 min), no analgesia can be seen immediately after the stress. We h
ave examined the two most obvious possibilities, but they do not seem
to be responsible for this fact. When morphine (1-5 mg/kg IP) is injec
ted in the S-240 situation, a potentiation of its analgesic effects is
seen, so that a desensitization of mu opioid receptors is unlikely. O
n the other hand, although cortisol (3-30 mg/kg IP) inhibits the analg
esic response to S-80, metyrapone (40 and 80 mg/kg IP) and cortexolone
(3-18 mg/kg IP) do not cause S-240 to be analgesic. Thus, an increase
of endogenous glucocorticoids released during the long-duration stres
s does not seem responsible for the lack of analgesia after S-240.