Behavioral changes following antisense oligonucleotide-induced reduction of organic cation transporter-3 in mice.
The organic cation transporter-3 (OCT3) can transport monoamines, similar to neuronal monoamine transporters. Due to the lack of selective ligands, however, the functional role of OCT3 is still unknown. Thus, we investigated behavioral effects of antisense against OCT3 (AS) in mice. AS (0.075-0.25 microg/0.25 microl/h, for 7 days) dose-dependently decreased immobility time. Moreover, although neither AS (0.075 microg/0.25 microl/h, for 7 days) or imipramine (4 mg/kg, i.p.) were effective, imipramine (4 mg/kg, i.p.) significantly decreased immobility time in mice treated with AS (0.075 microg/0.25 microl/h, for 7 days). Additionally, AS (0.25 microg/0.25 microl/h, for 7 days) significantly increased locomotor activity induced by methamphetamine (1 mg/kg, s.c.), but did not affect spontaneous locomotor activity. These results suggest that OCT3 might become a novel molecular target to treat depression and other diseases related to monoaminergic neuronal systems.
Kitaichi
Kiyoyuki
K
Department of Medical Technology, Nagoya University School of Health Sciences, 1-1-20, Daikominami, Nagoya 461-8673, Japan. kitaichi@met.nagoya-u.ac.jp
Fukuda
Masaya
M
Nakayama
Hironao
H
Aoyama
Nagisa
N
Ito
Yukiko
Y
Fujimoto
Yohei
Y
Takagi
Kenji
K
Takagi
Kenzo
K
Hasegawa
Takaaki
T
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D015153:Blotting, Western; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007099:Imipramine / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D029362:Organic Anion Transporters, Sodium-Independent / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D013550:Swimming / Q000523:psychology
D000929:Antidepressive Agents, Tricyclic; D000697:Central Nervous System Stimulants; D016376:Oligonucleotides, Antisense; D029362:Organic Anion Transporters, Sodium-Independent; C114338:organic anion transport protein 3; D008694:Methamphetamine; D007099:Imipramine