THE ROLE OF ENDOGENOUS OPIOIDS AS MEDIATORS OF THE HYPOTHERMIC EFFECTS OF INTRATHECALLY ADMINISTERED CALCIUM AND CALCITONIN-GENE-RELATED PEPTIDE IN MICE

To the authors' knowledge, the effect of i.t. administered calcium on thermoregulation in mice has not been investigated. Calcium administra tion (i.t.) induced hypothermia in mice. It was found that calcitonin gene-related peptide (CGRP) (i.t.) also produced hypothermia. Because opioids have well documented thermoregulatory effects, the authors eva luated whether the hypothermia induced by calcium and CGRP was the res ult of the release of opioids. Calcium induced hypothermia at differen t ambient temperatures (4-degrees-C, 22-degrees-C and 30-degrees-C) in intact mice. Similarly treated spinalized mice maintained body temper ature. Using laser Doppler flowmetry, there was a significant increase in blood flow in the tails of calcium-injected mice vs. those of vehi cle-injected mice. Both naloxone and naltrindole failed to block the h ypothermic effects of calcium (i.t.). Nor-binaltorphimine (i.t.) signi ficantly blocked calcium (i.t.)-induced changes in body temperature. C GRP (i.t.) produced hypothermia for 15 hr postinjection, with the maxi mum decrease at 3 hr. CGRP induced hypothermia in intact and sham-lesi oned mice but not in spinalized mice. CGRP (i.c.v.) also produced hypo thermia (onset, 15-min postinjection) followed by the peak effect at 1 hr with recovery to baseline temperature by 2 hr. Subthreshold doses of calcium and CGRP given in combination produced greater than additiv e hypothermia. The hypothermic effects of CGRP were reversed by naloxo ne, naltrindole and nor-binaltorphimine. CGRP produced significant hyp othermia in both morphine-tolerant and nontolerant mice. Chronic admin istration of CGRP in nontolerant and morphine-tolerant mice did not al ter hypothermia after pretreatment with CGRP (i.t.). Taken together, t hese data indicate that the mechanisms of action of both calcium and C GRP involve interaction with endogenous opioid systems and the hypothe rmia induced by both drugs includes a supraspinal component.