The expression of methiopropamine-induced locomotor sensitization requires dopamine D2, but not D1, receptor activation in the rat.
Methiopropamine (MPA) is a structural analog to methamphetamine and is categorized as a novel psychoactive substance that needs to be controlled. However, no study has been performed to determine whether MPA actually develops an addiction-like behavior similar to those arising from other psychomotor stimulants. Thus, we attempted to determine whether MPA produces locomotor sensitization in a manner similar to amphetamine. In the first experiment, rats were pre-exposed to either saline or one of three different doses of MPA (0.2, 1.0, or 5.0mg/kg, IP) with a total of four injections, respectively. After a 2-week withdrawal period, when they were challenged with the same dose of MPA, only the group that was pre-exposed to high dose of MPA (5.0mg/kg) showed sensitized locomotor activity. In the second experiment, all rats were pre-exposed to MPA (5.0mg/kg) only. Interestingly, the expression of MPA-induced locomotor sensitization was inhibited by a pre-injection of a dopamine D2 receptor antagonist, eticlopride (0.05mg/kg, IP), though not by a dopamine D1 receptor antagonist, SCH23390 (0.01mg/kg, IP). These results suggest that repeated injection of MPA in the rat provokes certain neuronal changes involving specific, likely D2, dopamine receptor-mediated pathways that contribute to the expression of MPA-induced locomotor sensitization.
Department of Physiology, Brain Korea 21 Plus Project for Medical Science, Brain Research Institute, Yonsei University College of Medicine, Seoul 120-752, South Korea.
Hyung Shin
HS
Yoon
Department of Physiology, Brain Korea 21 Plus Project for Medical Science, Brain Research Institute, Yonsei University College of Medicine, Seoul 120-752, South Korea.
Wen Ting
WT
Cai
Department of Life and Nanopharmaceutical Sciences & Department of Pharmacy, College of Pharmacy, Kyung Hee University, Seoul 130-701, South Korea.
Young Hun
YH
Lee
Department of Life and Nanopharmaceutical Sciences & Department of Pharmacy, College of Pharmacy, Kyung Hee University, Seoul 130-701, South Korea.
Kyung Tae
KT
Park
Department of Life and Nanopharmaceutical Sciences & Department of Pharmacy, College of Pharmacy, Kyung Hee University, Seoul 130-701, South Korea.
Yong Sup
YS
Lee
Department of Physiology, Brain Korea 21 Plus Project for Medical Science, Brain Research Institute, Yonsei University College of Medicine, Seoul 120-752, South Korea. Electronic address: jkim1@yuhs.ac.
Jeong-Hoon
JH
Kim
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D015259:Dopamine Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D008694:Methamphetamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D012457:Salicylamides / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology*
C583008:1-(2-thienyl)-2-(methylamino)propane; D001552:Benzazepines; D000697:Central Nervous System Stimulants; C000607792:DRD2 protein, rat; D015259:Dopamine Agents; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C534628:SCH 23390; D012457:Salicylamides; D013876:Thiophenes; D008694:Methamphetamine; C045989:eticlopride
Eticlopride; Locomotor sensitization; Methiopropamine; SCH23390