title: Dopamine D(3) receptor antagonist SB-277011A inhibits methamphetamine self-administration and methamphetamine-induced reinstatement of drug-seeking in rats.
abstract: We have previously reported that selective blockade of brain dopamine D(3) receptors by SB-277011A significantly attenuates cocaine self-administration and cocaine-induced reinstatement of drug-seeking behavior. In the present study, we investigated whether SB-277011A similarly inhibits methamphetamine self-administration and methamphetamine-induced reinstatement to drug-seeking behavior. Male Long-Evans rats were allowed to intravenously self-administer methamphetamine (0.05 mg/kg/infusion) under fixed-ratio 2 (FR2) or progressive-ratio (PR) reinforcement conditions, and some rats were tested for methamphetamine-induced reinstatement of drug-seeking behavior after extinction of self-administration. The effects of SB-277011A on each of these methamphetamine-supported behaviors were then tested. Acute intraperitoneal (i.p.) administration of SB-277011A failed to alter methamphetamine self-administration under FR2 reinforcement, but significantly lowered the break-point for methamphetamine self-administration under PR reinforcement. SB-277011A also significantly inhibited methamphetamine-triggered reinstatement of extinguished drug-seeking behavior. Overall, these data show that blockade of dopamine D(3) receptors by SB-277011A attenuates the rewarding and incentive motivational effects of methamphetamine in rats, supporting the development of selective dopamine D(3) antagonists for the treatment of methamphetamine addiction.
authors.affiliation: National Institute on Drug Abuse, Intramural Research Program, Baltimore, MD 21224, United States. ahigley@scripps.edu
authors.forename: Amanda E
authors.initials: AE
authors.lastname: Higley
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Kiefer
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.forename: József
authors.initials: J
authors.lastname: Gaál
authors.forename: Zheng-Xiong
authors.initials: ZX
authors.lastname: Xi
authors.forename: Eliot L
authors.initials: EL
authors.lastname: Gardner
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D004305:Dose-Response Relationship, Drug; D058999:Drug-Seeking Behavior / Q000187:drug effects*; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage* / Q000494:pharmacology*; D009570:Nitriles / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D050637:Receptors, Dopamine D3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012646:Self Administration; D044005:Tetrahydroisoquinolines / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D009570:Nitriles; D050637:Receptors, Dopamine D3; C409982:SB 277011; D044005:Tetrahydroisoquinolines; D008694:Methamphetamine