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.
BACKGROUND
The monoamine oxidase inhibitor (MAOI) clorgyline, blocks locomotor sensitization to the D(2)/D(3) 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 I(2) and sigma receptors, which could account for its effects on quinpirole sensitization.


OBJECTIVE
To examine whether the effect of clorgyline on quinpirole sensitization is attributed to stimulation of either I(2) or sigma receptors.


METHODS
In one experiment, rats received injections of the I(2) receptor agonist 2-BFI (0.2 mg/kg, IP) or vehicle, 90 min prior to each injection of quinpirole (0.5 mg/kg, SC, x 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 I(2) 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.


RESULTS
Like clorgyline, Ro 41-1049, but not 2-BFI, blocked the development of quinpirole-induced locomotor sensitization and induced instead sensitization of self-directed mouthing.


CONCLUSIONS
Because 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 I(2) 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.
Culver
Kirsten E
KE
Department of Psychiatry and Behavioural Neurosciences, McMaster University, Health Science Center, Room 4N82, 1200 Main Street West, Hamilton, Ontario, Canada L8N 3Z5.
Szechtman
Henry
H
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001572:Benzofurans / Q000008:administration & dosage / Q000494:pharmacology; D003010:Clorgyline / Q000008:administration & dosage / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology*; D004334:Drug Administration Schedule; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology; D054755:Imidazoline Receptors; D007279:Injections, Subcutaneous; D008024:Ligands; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D019257:Quinpirole / Q000494:pharmacology*; D051381:Rats; D020318:Rats, Long-Evans; D017448:Receptors, Dopamine D2 / Q000819:agonists; D050637:Receptors, Dopamine D3; D011955:Receptors, Drug / Q000819:agonists / Q000502:physiology*; D017480:Receptors, sigma / Q000502:physiology*; D013844:Thiazoles / Q000008:administration & dosage / Q000494:pharmacology
D001572:Benzofurans; D018491:Dopamine Agonists; C493595:Drd3 protein, rat; D007093:Imidazoles; D054755:Imidazoline Receptors; D008024:Ligands; D008996:Monoamine Oxidase Inhibitors; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D011955:Receptors, Drug; D017480:Receptors, sigma; D013844:Thiazoles; D019257:Quinpirole; C063456:Ro 41-1049; C103723:2-(2-benzofuranyl)-2-imidazoline; D003010:Clorgyline; D004298:Dopamine