Sensitization of apomorphine-induced stereotyped behavior in mice is context dependent

Rationale: The role of the environment in the sensitization of the stereoty ped behavioral effects of apomorphine is unclear, since sensitization of th is drug effect has either been difficult to demonstrate or has been shown t o occur with a low but not a higher dose of apomorphine. Objectives: The pr esent study was designed to determine whether sensitization of the stereoty ped behavioral effects induced by a single dose of apomorphine is dependent on environmental context. Methods: CF-1 mice were pretreated with apomorph ine or vehicle under different environmental conditions and tested for ster eotyped behavior after apomorphine challenge. Animals were scored positivel y for stereotyped behavior if they remained stationary and exhibited repeti tive head and/or fore-limb movements, and data are reported as the percenta ge of mice rated as positive for stereotyped behavior. Results: When mice w ere pretreated with 40 mg/kg apomorphine and later tested in the same envir onment, the dose-response curve for stereotyped behavior elicited by apomor phine was shifted threefold to the left 48 h after pretreatment, and this s ensitization persisted for at least 28 days after pretreatment. Mice pretre ated with apomorphine did not have higher brain levels of apomorphine after administration of the test dose of apomorphine. When the pretreatment envi ronment was different from the test environment, mice did not exhibit sensi tization to apomorphine. Conclusions: These results show that pre-exposure to a single high dose of apomorphine induces a long-lasting sensitization o f apomorphine-induced stereotyped behavior that is context dependent. Since apomorphine directly activates dopamine receptors, these observations sugg est that a mechanism located postsynaptic to dopamine neurons may be respon sible for sensitization of stereotyped behavior.