The dopamine D3 receptor partial agonist CJB090 and antagonist PG01037 decrease progressive ratio responding for methamphetamine in rats with extended-access.
Previous work suggests a role for dopamine D3-like receptors in psychostimulant reinforcement. The development of new compounds acting selectively at dopamine D3 receptors has opened new possibilities to explore the role of these receptors in animal models of psychostimulant dependence. Here we investigated whether the dopamine D3 partial agonist CJB090 (1-10 mg/kg, i.v) and the D3 antagonist PG01037 (8-32 mg/kg, s.c.) modified methamphetamine (0.05 mg/kg/injection) intravenous self-administration under fixed- (FR) and progressive- (PR) ratio schedules in rats allowed limited (short access, ShA; 1-hour sessions 3 days/week) or extended access (long access, LgA; 6 hour sessions 6 days/week). Under a FR1 schedule, the highest dose of the D3 partial agonist CJB090 selectively reduced methamphetamine self-administration in LgA but not in ShA rats, whereas the full D3 antagonist PG01037 produced no effect in either group. Under a PR schedule of reinforcement, the D3 partial agonist CJB090 reduced the maximum number of responses performed ('breakpoint') for methamphetamine in LgA rats at the doses of 5 and 10 mg/kg, and also it produced a significant reduction in the ShA group at the highest dose. However, the D3 full antagonist PG01037 only reduced PR methamphetamine self-administration in LgA rats at the highest dose of 32 mg/kg with no effect in the ShA group. The results suggest that rats might be more sensitive to pharmacological modulation of dopamine D3 receptors following extended access to methamphetamine self-administration, opening the possibility that D3 receptors play a role in excessive methamphetamine intake.
Orio
Laura
L
The Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA 92037, USA. lorio@scripps.edu
Wee
Sunmee
S
Newman
Amy H
AH
Pulvirenti
Luigi
L
Koob
George F
GF
D019969:Amphetamine-Related Disorders / Q000503:physiopathology*; D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D015259:Dopamine Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D007262:Infusions, Intravenous; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D009042:Motivation / Q000187:drug effects*; D010879:Piperazines / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D050637:Receptors, Dopamine D3 / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000502:physiology; D012055:Reinforcement Schedule; D012646:Self Administration
D001549:Benzamides; D000697:Central Nervous System Stimulants; D015259:Dopamine Agents; C497150:N-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)but-2-enyl)-4-pyridine-2-ylbenzamide; C545833:N-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butyl)-4-(pyridin-2-yl)benzamide; D010879:Piperazines; D011725:Pyridines; D050637:Receptors, Dopamine D3; D008694:Methamphetamine
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