INDUCTION OF SENSITIZATION TO HYPERACTIVITY CAUSED BY MORPHINE IN MICE - EFFECTS OF POST-DRUG ENVIRONMENTS

Mice given five repeated administrations of morphine (10 mg/kg sc) at 3 day intervals in a round tilting-type activity cage (20 cm in diamet er) or round spaces 15-30 cm in diameter with fixed floor showed almos t the same lever of ambulatory sensitization to morphine. Whereas, mic e given morphine in the same schedule in spaces 4 and 12 cm, but not 6 and 9 cm, in diameter demonstrated a partial increase in the sensitiv ity to morphine. Furthermore, mice given morphine five times in a tran sparent cage (20W x 25L x 15H cm) with woodchip bedding, that was the same as the home cage, showed a weak and strong ambulatory sensitizati on when they were placed in group of ten and singly, respectively, for 3 h after each morphine administration. Repeated administrations of s aline to mice in the space 4 cm in diameter resulted in increased sens itivity to morphine. However, the pretreatment with saline in the othe r environments (activity cage, spaces 6-30 cm in diameter with fixed f loor, and home cage-like cage in which mice were placed singly or in g roup of ten) did not change the sensitivity to morphine. These results suggest that repeated experience of pharmacological effect of morphin e and the resultant ambulation is one of the most important factors fo r induction of strong ambulatory sensitization to morphine in mice. It is estimated that a space 15 cm in diameter, which corresponds to 2-2 .5 times as long as the body length without tail is a minimum requirem ent for induction of strong ambulatory sensitization to morphine. In c ontrast, even though mice are placed in a sufficient space for ambulat ion, an interference of ambulation by the other mice acts to inhibit t he induction of ambulatory sensitization. It is also suggested that a strong stress caused by restraint is responsible for significant incre ase in sensitivity to morphine. (C) 1997 Elsevier Science Inc.