[Cocaine toxicity, enhancing effects in grouped mice and mechanism on behavioral characteristics]

A marked increase in lethality in grouped mice (group toxicity) following the administration of methamphetamine, a central nervous stimulant, has been well known. Pharmacological effects, behavioral characteristics and toxicities of cocaine are fairly similar to those of methamphetamine. Thus, in this study, the possibility of producing group toxicity induced by cocaine and the participation of biogenic amines and neurotransmitters in the production of behavioral sensitization with cocaine was investigated in ddY male mice. 1) In acute experiment, LD50s of cocaine were not different significantly between control (5 mice) and grouped mice (20 mice), and following continuous administration of cocaine (40 and 50 mg/kg, once a day for 10 days) lethal cases were not observed in control, but mortality was calculated to about 20 and 60% in grouped mice, respectively. 2) The number of deaths was related to environmental condition that mice were restricted. And in the stronger restricted condition, the number of deaths increased. 3) The number of deaths was highly dependent on the environmental temperature and the doses. 4) The repeated administration of cocaine produced the behavioral sensitization in the non-restricted mice but not in the restricted mice. 5) The drugs that changed amines or neurotransmitters inhibited the effects of cocaine in the first administration, but following the repeated administration behavioral sensitization was produced gradually. It is concluded that group toxicity was induced by cocaine. It is also considered that the behavioral sensitization with cocaine was intricately related to many amines or transmitters.