Ethological analysis of morphine withdrawal with different dependence programs in male mice

Abstract

This work was performed to clarify the differences between a long or short development of morphine dependence as well as between a recently installed or a long-term dependence. Morphine withdrawal in rats is a well-characterized phenomenon but this is not so in mice. A study of the principal withdrawal signs have been performed in mice, evaluating their specificity and particular profile of appearance in each type of dependence. Mice were divided into two groups that received increasing doses of morphine every 24 h, three groups that received increasing doses of morphine twice a day for 3 days, and a control group that received saline. Naloxone-induced opiate withdrawal was evaluated following short-term exposition to morphine [Test 1 (T1)--saline and Test 2 (T2)--naloxone] and long-term exposition to morphine [Test 3 (T3)--naloxone and Test 4 (T4)--saline]. Morphine administration twice a day is more effective in inducing opiate dependence than once a day, and with the latter, the duration of morphine exposure increases the intensity of withdrawal signs. Weight loss, diarrhea, body shakes, jumping, paw tremor, ptosis, piloerection, and the modified Gellert-Holtzman scale for mice are specific patterns of naloxone-induced withdrawal. The first four signs allow the discrimination between different levels of opiate dependence. Body care, piloerection, and the modified Gellert-Holtzman scale could be useful to detect conditioned withdrawal.