Environment modifies the expression of behavioral sensitization produced by methamphetamine: behavioral and neurochemical studies.

Effects of environmental modulation of methamphetamine (MA)-induced behavior on the establishment and mode of expression of behavioral sensitization were examined. Rats received daily injection of MA for 10 days (1mg/kg, s.c.). Half of them were immediately returned to the home cage (home cage group) and the other half were individually confined in a cylinder with a diameter of 13cm placed inside the home cage for 3h after each injection (small cage group). Gross observations revealed that rats which received MA in the small cage did not locomote but showed sniffing and rearing. The third group received saline in the home cage (saline control group). After a 7-8 day or 17-18 day withdrawal period, all groups were injected with MA (1mg/kg or 0.5mg/kg) in their home cages. The home cage group showed significant enhancement in horizontal motor activity compared to the saline control group, indicating the establishment of locomotor sensitization. In contrast, the small cage group showed no or slight enhancement in the motor activity. However, they showed significantly more stereotyped behavior compared to both the saline control and the home cage groups. Microdialysis studies revealed no enhancement in the ability of MA to increase dopamine release from the nucleus accumbens in either the home or the small cage group compared to the saline control group, when examined after either a 7-8 day or a 17-18 day withdrawal period. These results suggest that environmental modulation of actual movement under the stimulant effect modifies the pattern and character of the stimulant-induced behavior in sensitized animals. The neurochemical basis of the establishment of behavioral sensitization and the environmental modification of its expression remain unknown.