Pharmacology B~ochemtstry& Behavior, Vol 26, pp 539-542 Copyright © PergamonJournalsLtd , 1987 Pnntedm the U S A 0091-3057/87 $3 130+ 00 Short-Term and Delayed Behavioral Effects of Pre- and Post-Weaning Morphine in Mice I ENRICO ALLEVA AND GIOVANNI LAVIOLA Section of Neurobehavloral Pathophyslology, Laboratorlo di Flslopatologia dl Organo e di Sistema Istituto Superiore di Saint6, V.le Regina Elena, 299, 1-00161 Roma, Italy Received 15 April 1986 ALLEVA, E AND G LAVIOLA Short-term and delayed behavtoral effects of pre- and post-weamng morphine tn mtce PHARMACOL BIOCHEM BEHAV 26(3) 539--542, 1987 --Ninety mouse pups of the CD-1 outbred strata were used to assess actlwty (Vanmex Activity Meter, Columbus Instr, OH) and analgesia (hot plate) after morphine hydrochlonde given IP either on days 14-16 (preweanhngs) or on days 21-23 (postweanhngs) In preweanhngs morphine depressed activity already at the lowest dose tested (0 5 mg/kg), and higher doses (1, 5, and 10 mg/kg) d~d not produce a s~gmficantly larger effect Activity of postweanhngs was not depressed until a very h~gh dose (20 mg/kg) By contrast, morphine produced clear analgesic effects at all doses m both preweanhngs (day 14) and postweanhngs (day 21) Around day 70, activity and hot-plate tests m the no-drug state showed no differences due to prior treatment, except for the fact that hot-plate latenc~es of m~ce previously ~njected wtth sahne as preweanhngs were h~gher than those of all other groups Twenty-four hr later the tests were repeated after morphine mject~on (10 mg/kg), and showed a s~gmficantly greater depression of activity m m~ce prewously exposed as preweanhngs On the other hand, all groups previously exposed to morphine at e~ther the pre- or the post-weanhng stage showed tolerance to the analgesic effect of the drug These developmental profiles confirm that op~oid systems contribute to the modulation of activity by mechanisms which are at least m part separate from those mediating analgesia Mouse behavioral development Morphine analgesia Environmentallyreduced analgesia (EIA) Hot plate Locomotor actiwty Adult tolerance SYSTEMIC admtnistrat~on of morphine to altrlc~al rodents at d~fferent postnatal stages results in quite different physi- ological and behavioral changes [6, 14, 15, 17, 19, 20] Speof- ~cally, the analgesic effect of the drug m rats increases from early postnatal period until about day 15 [6,14] in parallel to a rapid rise in the number of ~-receptors [19] In the subse- quent period, drug sens~t~wty declines [6,15] in parallel to the reduction of general drug toxicity [17], and these changes are apparently related to the maturation of the blood/brain bar- her [6,17] Locomotor actlwty ~s also differentially affected by mor- phine as a function of postnatal age. One study showed a reduction of activity ~n rats of ten days, and either no ef- fects or actiwty enhancements at later ages [9] In another study, Inbred mice of the C57B1/6 strain showed mmnly hyperactivity during ontogeny, except for a brief period (days 20-22) in which the drug produced a marked catatoma [11] More recently, attention has been given to the proactive effects of postnatal morphine exposure on subsequent re- sponding to the drug For example, extended morphine ad- ministration ~n rats from birth to weaning produced tolerance to the analgesic and hypoactivatmg effects of the drug at 22 days w~thout, however, any appreciable effect on /x-receptors prohferatton [7]. The same investigators also showed that a single dose of morphine given to newborn rats sufficed to produce a similar change in sensitivity 26 days later. Th~s change faded to appear in pups ~njected only a few days later, that is, e~ther on day 5, 9, or 13 [8]. The present work' was designed to assess the effects of different doses of morphine on pain sensitivity and locomo- tor activity of mice before and after weaning, and the conse- quences of such exposure on adult sensitivity to the same drug. Animals were treated and tested for three consecutive days either dunng the last part of the pre-visual stage (pre- weanhngs, days 14-16, eye opening is completed on day 17 ~n the strain used [5]), or starting on the day after weaning (postweanhngs, days 21-23) These treatment periods were chosen also on the bas~s of a previous study which showed that mouse pups of these two ages have quite different pat- terns of activity, habituation, and response to model drugs such as amphetamine and scopolamine [2]. All animals were retested at about 70 days of age for actiwty, pain reactivity, and morphine effects thereon ~Part of the data on activity and analgesia in ~mmature mice were presented at the IX European Neurosoence Association congress (Oxford, U K , 8-12 September, 1985) [4] 539