Naloxone-precipitated abstinence in mice, rats and gerbils acutely dependent on morphine

Acute dependence on a single dose of morphine in mice, rats and gerbils was assessed by observing several signs of abstinence precipitated by various doses of naloxone, diprenorphine and Mr 2097. In mice and rats acutely dependent on morphine, naloxone, diprenorphine and Mr 2097 precipitated dose-dependently the signs of abstinence such as jumping, urination, teeth chattering, chewing, paw shakes, head shakes and ptosis. In these two species, the precipitation of these signs were mediated by stereospecific opiate receptors, as Mr 2096, the non-antagonistic isomer of Mr 2097, did not precipitate any of them. In gerbils acutely dependent on morphine, naloxone precipitated urination, teeth chattering, chewing, paw shakes, head shakes, "wet dog" shakes, yawning and writhing. In naive animals of all three species, the opioid antagonists produced varying degrees of "abstinoid" signs. The precipitated withdrawal might be the result of "abstinoid" effects superimposed on real abstinence signs. High doses of naloxone and diprenorphine showed a regression of "abstinoid" signs probably because of interfering morphinomimetic properties. The present data indicate that these three rodents may be successfully employed in the rapid identification of drugs to produce morphine-like dependence or to precipitate withdrawal.