Kuribara H
Laboratory of Development, Wakanyaku Medical Institute Ltd, Gunma, Japan.
J Pharm Pharmacol. 1998 Mar;50(3):303-9. doi: 10.1111/j.2042-7158.1998.tb06865.x.
Repeated administration of CNS stimulants such as amphetamines and cocaine induces behavioural sensitization which can be influenced by the animal's environment. This study has evaluated the effect of restraint on the development and maintenance of ambulatory sensitization to methamphetamine and cocaine in mice. Subcutaneous administration of the CNS stimulants methamphetamine (2 mg kg(-1)) and cocaine (20 mg kg(-1)) seven times at three-day intervals resulted in ambulatory sensitization when the mice were placed in 20-cm diameter activity cages after each dose of the drug. However, if methamphetamine or cocaine was administered when the mice were in small jars (6-cm diameter) in which expression of ambulation, but not of circling and rearing, was completely restricted, the development of ambulatory sensitization was retarded or inhibited, with circling behaviour concurrently increased, when subsequent repeated doses of the drug were administered in the activity cage. Subsequent repeated treatment of ambulatory-sensitized mice with the drug or saline when the mice were in the jars did not change the levels of the ambulatory sensitization or the circling behaviour. These results suggest that the mice are sensitized to the behavioural effect of CNS stimulants which can be expressed in the environment in which the drug is administered. It is also considered that the established sensitization is strongly retained and is responsible for retardation or suppression of the development of sensitization to other behavioural stimulant effects.
反复给予中枢神经系统兴奋剂，如苯丙胺和可卡因，会诱发行为敏化，这种敏化会受到动物环境的影响。本研究评估了限制环境对小鼠甲基苯丙胺和可卡因动态行为敏化的发展及维持的影响。每隔三天皮下注射中枢神经系统兴奋剂甲基苯丙胺（2毫克/千克）和可卡因（20毫克/千克），共注射七次，每次给药后将小鼠置于直径20厘米的活动笼中，结果导致了动态行为敏化。然而，如果在小鼠置于小罐（直径6厘米）中时给予甲基苯丙胺或可卡因，在小罐中行走的表现完全受到限制，但转圈和竖毛行为不受限，那么当随后在活动笼中重复给药时，动态行为敏化的发展会延迟或受到抑制，同时转圈行为增加。随后在小鼠置于小罐中时，用药物或生理盐水对动态行为敏化的小鼠进行重复处理，并没有改变动态行为敏化的水平或转圈行为。这些结果表明，小鼠对中枢神经系统兴奋剂的行为效应产生了敏化，这种敏化可在给药环境中表现出来。还认为，已建立的敏化会强烈保留，并导致对其他行为刺激效应的敏化发展延迟或受到抑制。
