title: A dose-response study of separate and combined effects of the serotonin agonist 8-OH-DPAT and the dopamine agonist quinpirole on locomotor sensitization, cross-sensitization, and conditioned activity.
abstract: Chronic treatment with the dopamine D2/D3 agonist, quinpirole, or the serotonin 1A agonist, 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT), induces behavioral sensitization. It is not known whether both drugs produce sensitization through a shared mechanism. Here, we examine whether quinpirole and 8-OH-DPAT show cross-sensitization and impact sensitization, as would be expected from shared mechanisms. Male rats (N=208) were assigned randomly to 16 groups formed by crossing four doses of quinpirole (0, 0.03125, 0.0625, or 0.125 mg/kg) with four doses of 8-OH-DPAT (0, 0.03125, 0.625, or 0.125 mg/kg). After a course of 10 drug treatments administered twice per week in locomotor activity chambers, all groups were challenged on separate tests with quinpirole (0.1 mg/kg), 8-OH-DPAT (0.1 mg/kg), or saline, and locomotor activity was evaluated. Challenge tests with quinpirole and 8-OHDPAT showed no cross-sensitization between the drugs. Chronic quinpirole (0.125 mg/kg) administration induced a sensitized quinpirole response that was attenuated dose-dependently by chronic 8-OH-DPAT cotreatment. Cotreatment with quinpirole (0.0625 mg/kg) and 8-OH-DPAT (all doses) induced quinpirole sensitization. Chronic 8-OH-DPAT (0.125 mg/kg) induced a sensitized 8-OHDPAT response that was prevented by chronic cotreatment with the lowest but not the highest dose of quinpirole. Cotreatment with 8-OHDPAT (0.0625) and quinpirole (0.125 mg/kg) induced sensitization to 8-OH-DPAT. The saline challenge test showed elevated locomotor activity in chronic quinpirole (0.125 mg/kg) and 8-OHDPAT (0.0625, 0.125 mg/kg) alone groups, and in seven of nine cotreated groups. The absence of cross-sensitization suggests separate mechanisms of sensitization to quinpirole and 8-OH-DPAT. Cotreatment effects suggest that induction of sensitization can be modulated by serotonin 1A and D2/D3 activity.
authors.affiliation: Department of Psychiatry and Behavioral Neurosciences, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Eric F
authors.initials: EF
authors.lastname: Johnson
authors.forename: Henry
authors.initials: H
authors.lastname: Szechtman
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008124:Locomotion / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D019257:Quinpirole / Q000008:administration & dosage / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D020318:Rats, Long-Evans; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000187:drug effects; D050637:Receptors, Dopamine D3 / Q000187:drug effects; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D018491:Dopamine Agonists; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D017366:Serotonin Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; D019257:Quinpirole; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin