The antinociceptive and hypothermic effects of intracisternal administration of 11 endogenous neuropeptides and morphine were evaluated in mice. Of the substances tested, only neurotensin (NT) and l-endorphin exerted significant antinociceptive and hypothermic effects; NT was the most potent in inducing hypothermia whereas l-endorphin was the most potent antinociceptive agent via this route of administration.Both NT and f3-endorphin were, on a molar basis, considerably more potent antinociceptive agents than morphine, [Metlenkephalin, or [Leujenkephalin. NT-induced analgesia and hypothermia both were significantly dose-dependent. Substance P was found to produce significant hyperalgesia and hyperthermia. Bombesin produced a significant hypothermic effect, whereas somatostatin and luteinizing hormone-releasing hormone (luliberin) produced hyperthermia. None of the other peptides studied [bradykinin, thyrotropin- In recent years, several peptides endogenous to brain have been found to produce various effects when administered either systemically or directly into the central nervous system (1, 2). Considerable attention has been focused on the endorphins and enkephalins which are endogenous opiate-like peptides that produce antinociception (3-5), hypothermia (6), and various other behavioral effects (7). In addition, they bind avidly to brain opiate receptors (8). Neurotensin (NT) and bombesin are potent hypothermic agents after intracerebroventricular administration in rats and mice (9, 10). Furthermore, peptides other than the endorphins and enkephalins have been reported to produce significant analgesia after direct intracerebral injection. These include NT, bradykinin, and substance P (11)(12)(13)(14).The purpose of the present study was to evaluate the antinociceptive properties and the effect on colonic temperature of 11 endogenous neuropeptides and morphine after intracisternal administration in mice. Of particular interest was the evaluation of the dose-response relationship of NT-induced antinociception.
MATERIALS AND METHODSAntinociceptive activity was measured in adult male albino Swiss-Webster mice (25-30 g) by the tail-immersion test developed for use in rats by Janssen and coworkers (15) as modified for use in mice by Sewell and Spencer (16). Groups of mice (n > 6 per group) were lightly anesthetized with ether and injected intracisternally with vehicle (0.9% NaCl, pH 7.5) or with one of the following peptides: NT, substance P, thyrotropin-releasing factor (thyroliberin), luteinizing hormone-releasing factor (luliberin), bradykinin, melanocyte-stimulating hormone-release inhibiting factor (melanostatin), somatostatin, 3-endorphin, [Met]enkephalin, [Leu]enkephalin, and bombesin. Morphine sulfate was also tested. Thyroliberin (lot 31-330-AL) was provided by Abbott; NT (lot 14-296-10), f-endorphin (lot 28-111-30), and bombesin (lot 42-206-20) were generously supplied by Jean E. Rivier (The Salk Institute, La Jolla, CA). All the other peptides and morphine were purchased commercially: luliberin...