Prodynorphin-derived
peptides were tested for their effects on body temperature after intracerebroventricular administration to unrestrained male rats.
Dynorphin A (Dyn A) (5 and 10 nmol) and
Dynorphin A-(1-32) (Dyn A-(1-32) (2.5 and 5 nmol) lowered body temperature with a maximum approximately 30 min after administration. Dyn B (up to 50 nmol) did not induce
hypothermia. Lower doses of all
peptides did not alter body temperature. The hypothermic effect was significantly, but not completely prevented by
MR1452 (30 nmol), a preferential antagonist of the
kappa receptor, administered intracerebroventricularly.
Naloxone, a
mu receptor antagonist,
naltrexone, its long acting analog up to doses of 100 nmol, as well as
MR1453, the (+)-enantiomer of kappa antagonist
MR1452 with no
opioid binding properties, did not prevent the hypothermic effect. Moreover, episodic barrel rolling and bizarre postures elicited by Dyn A and Dyn A-(1-32) were reduced in rats pretreated i.c.v. with
MR1452 (30 nmol), but not with
naloxone (up to 100 nmol). Interestingly, des-Tyr-
Dynorphin A (
Dyn A-(2-17)), a fragment with virtually no
opioid binding potential, was 4 times less potent that Dyn A in inducing
hypothermia. These findings are consistent with the hypothesis that
prodynorphin-derived
peptides effects are not exclusively
opioids in nature.