A switch mechanism between locomotion and mouthing implicated in sensitization to quinpirole in rats

Rationale: Chronic treatment with the monoamine oxidase inhibitor (MAOI) cl orgyline, blocks locomotor sensitization to the D2/D3 dopamine agonist quin pirole. It is unknown whether this blockade occurs via inhibition of the MA O enzyme or by another mechanism. Objectives: While clorgyline and moclobem ide are equally effective MAOIs, only clorgyline has a high affinity for th e MAOI-displaceable quinpirole binding site (MQB). This study compares the effects of both drugs on quinpirole sensitization. Methods: To examine deve lopment of sensitization, rats received clorgyline (1 mg/kg/day), moclobemi de (5 mg/kg/day), or vehicle via osmotic mini-pumps and were injected with quinpirole (0.5 mg/kg, s.c.) or saline every 3 days; locomotor and mouthing activity was recorded for each of the eight injections. A similar protocol was used to examine the expression of sensitization in rats previously sen sitized to quinpirole. Results: Clorgyline, but not moclobemide, blocked th e development of locomotor sensitization to quinpirole. Clorgyline, but not moclobemide, blocked the sensitized locomotor response to quinpirole follo wing the 25th day of treatment. Mouthing showed sensitization in quinpirole -treated rats co-treated with clorgyline, but not moclobemide; this sensiti zed mouthing was predominantly directed towards self. Clorgyline and moclob emide equally inhibited MAO-A and had equal effects on tissue concentration s of dopamine, 3,4-dihydroxyphenylacetic acid, and serotonin in the striatu m. Conclusions: Clorgyline (1) inhibits the development and the maintenance of locomotor sensitization to quinpirole by a mechanism that does not invo lve MAO and (2) changes the sensitized response to quinpirole from locomoti on to mouthing. We suggest that clergy line affects the response to quinpir ole via MQB and that this site acts as a switch that selects the motor path way for sensitization to quinpirole.