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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 |
Authors: | Johnson EF Szechtman H |
Department: | Psychiatry & Behavioural Neurosciences |
Keywords: | 8-Hydroxy-2-(di-n-propylamino)tetralin;Animals;Behavior, Animal;Dopamine Agonists;Dose-Response Relationship, Drug;Locomotion;Male;Motor Activity;Quinpirole;Random Allocation;Rats;Rats, Long-Evans;Receptor, Serotonin, 5-HT1A;Receptors, Dopamine D2;Receptors, Dopamine D3;Serotonin Receptor Agonists |
Publication Date: | Aug-2016 |
Publisher: | Ovid Technologies (Wolters Kluwer Health) |
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. |
URI: | http://hdl.handle.net/11375/26817 |
metadata.dc.identifier.doi: | https://doi.org/10.1097/fbp.0000000000000219 |
ISSN: | 0955-8810 1473-5849 |
Appears in Collections: | Psychiatry & Behavioural Neurosciences Publications |
Files in This Item:
File | Description | Size | Format | |
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Johnson2016_ADoseResponseStudy_BP-15-194_R1 (1).pdf | Accepted version | 960.4 kB | Adobe PDF | View/Open |
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