Psychopharmacologia (Berl.) 41, 197-200 (1975) 9 by Springer-Verlag 1975 Original Investigations A Genetic Analysis of Morphine-Induced Running and Analgesia in the Mouse CLAUDIO CASTELLANO and ALBERTO OLIVERIO Laboratorio di Psicobiologia e Psicofarmacologia, Roma, Italy Received July 29, 1974; Final Version October 28, 1974 Abstract. A genetic analysis of morphine-induced analgesia behavioral measures and support that their mode of inher- and activity was conducted in mice belonging to the strains itance is characterized by dominance or partial dominance. BALB/cJ, C57BL/6J, DBA/2J and to their F1 and back- The biometric analysis conducted on the parental, F1 hybrid cross progenies. The results support previous findings show- and backcross populations indicates very clearly that the ing that a negative correlation is evident between these two effects of morphine are genetically determined. Key words: Morphine - Running - Analgesia - Genetic Analysis. A number of findings suggest that genetic factors play an important role in modulating the effects of mor- phine on different behavioral patterns. For example, it has been shown that it is possible to breed rats differ- ing in their sensitivity to morphine addiction (Nichols and Hsiao, 1967) and that various strains of inbred mice present different patterns of morphine addiction. When we consider the effects of opiates on the locomotor activity of mice wide variations between individual mice (Goldstein and Sheehan, 1969) or in- bred strains (Oliverio and Castellano, 1974) have been reported. The results of a previous study con- ducted in three inbred strains of mice indicated that both sensitivity and tolerance to opiate-induced anal- gesia and locomotor activity are genetically deter- mined. In particular, it was observed that the effects of opiates on running activity and analgesia were clearly dissociated, a negative correlation between the degree of running and analgesic responses caused by morphine being clearly evident in the strains consi- dered. For example the C57BL/6J strain presented the highest locomotor response, while the same strain was less sensitive to the analgesic effects of morphine. These findings were not due to strain differences in the reactivity to the hot plate since undrugged mice belonging to the three strains presented similar re- sponse latencies. The present experiment was designed to assess the mode of inheritance of morphine-induced analgesia and motor activity by using a diallel study in which three inbred strains and their F1 hybrids crosses were used. Biometric analysis and individual correlations between these two behavioral measures were also conducted by using the backcross between F1 mice and their two progenitor strains. The results indicate that the mode of inheritance of morphine-induced running or analgesia is characterized by dominance or partial dominance. Analysis of variance of the backcross populations also indicated that the effects of morphine are genetically determined. Finally, the findings of this study indicate the existence of signifi- cant negative correlations when the two behavioral measures are considered in the parental or hybrid strains or in individual mice belonging to the backcross populations. Method Subjects. The subjects were 100 male mice belonging to the strains BALB/cJ(B), C57BL/6J(C), DBA/2J(D) and to their reciprocal F1 progeny. Since no significant differences were evident between the reciprocal crosses BC and CB and CD and DC respectively (where the first letter of each hybrid refers to the female parent and the second to the male parent) the symbols C • B and C • D referring to the pooled reciprocal crosses are employed. The inbred strains were procured from the Jackson Laboratory, Bar Harbor, Maine. Each experimental group consisted of 10 mice. In order to produce subjects representing the back- cross populations F1 hybrids C x B and C • D mice were