Clorgyline-induced switch from locomotion to mouthing in sensitization to the dopamine D2/D3 agonist quinpirole in rats: role of sigma and imidazoline I2 receptors

RationaleThe monoamine oxidase inhibitor (MAOI) clorgyline, blocks locomotor sensitization to the D2/D3 dopamine agonist quinpirole and sensitizes self-directed mouthing behavior in rats by a mechanism independent of MAO inhibition. Clorgyline has a high affinity for imidazoline I2 and sigma receptors, which could account for its effects on quinpirole sensitization.ObjectivesTo examine whether the effect of clorgyline on quinpirole sensitization is attributed to stimulation of either I2 or sigma receptors.MethodsIn one experiment, rats received injections of the I2 receptor agonist 2-BFI (0.2 mg/kg, IP) or vehicle, 90 min prior to each injection of quinpirole (0.5 mg/kg, SC, × 8, twice weekly) or saline. A similar protocol was used to examine the effects of the MAOI Ro 41-1049 (10 mg/kg, SC) on quinpirole sensitization. Unlike clorgyline, Ro 41-1049 has no affinity for sigma or I2 sites. An initial experiment demonstrated that intermittent injections of clorgyline (1 mg/kg, SC) are as effective as a continuous clorgyline administration (1 mg/kg per day via osmotic mini-pump) on quinpirole sensitization.ResultsLike clorgyline, Ro 41-1049, but not 2-BFI, blocked the development of quinpirole-induced locomotor sensitization and induced instead sensitization of self-directed mouthing.ConclusionsBecause Ro 41-1049 produced the same effects as clorgyline, and 2-BFI had no effects on quinpirole sensitization, it is unlikely that clorgyline exerts its effects via an action at sigma or I2 receptors. Our results are consistent with the suggestion that clorgyline and Ro 41-1049 affect the behavioral response to quinpirole via the MAOI-displaceable quinpirole binding (MQB) site, and the hypothesis that the MQB site selects what motor output becomes sensitized to repeated injections of quinpirole.