Differential effects of clorgyline on sensitization to quinpirole in rats tested in small and large environments.

Rationale: Cotreatment with clorgyline shifts the development of sensitization to the D2/D3 dopamine receptor agonist quinpirole from locomotion to mouthing, an effect apparently unrelated to the monoamine oxidase inhibition property of clorgyline. This phenomenon was demonstrated in rats examined in small activity chambers. However, like with other psychostimulant drugs, sensitization to quinpirole is modulated by environmental context. It is not known whether the clorgyline cotreatment effect is likewise influenced by the environment.

Objective: To determine the generality of the clorgyline effect on behavioral sensitization by evaluating the effects of clorgyline cotreatment on sensitization to quinpirole in two different environments: a small activity chamber and a large open field.

Methods: Male rats received eight injections of quinpirole (0.5 mg/kg, twice weekly) in an open field or activity chamber; one group in each environment received a constant infusion of clorgyline (1 mg/kg/day via osmotic minipumps) while the other group served as the sham surgery control. For quinpirole injection 7 or 8, rats were tested in the alternate environment.

Results: In activity chambers, clorgyline cotreatment switched sensitization to quinpirole from locomotion to mouthing. In the open field, clorgyline cotreatment increased mouthing and expanded the explored space without a change in path stereotypy or the amount of locomotion compared to treatment with quinpirole alone.

Conclusions: Structure of the environment can modulate the clorgyline cotreatment effect on behavioral sensitization to quinpirole. The behavioral profiles produced by clorgyline cotreatment in the two environments resembled the behavioral effects observed with quinpirole and D1 agonist cotreatment. It is suggested that clorgyline cotreatment produces a behavioral profile characteristic of enhanced dopamine D1 and D2 receptor costimulation.