Involvement of sigma 1 receptors in methamphetamine-induced behavioral sensitization in rats.
MS-377 is a novel selective sigma(1) ligand, currently being developed for the treatment of schizophrenia. In the present study, we examined the effects of MS-377 on behavioral sensitization induced by subchronic treatment with methamphetamine. MS-377 was administered at doses of 1.875-15 mg/kg (p.o.), to rats, and methamphetamine was administered at doses of 2 mg/kg (i.p.), 60 min later once daily for 10 days. Repeated administration of methamphetamine caused enhanced stereotypy, and behavioral sensitization was developed. MS-377 did not affect the acute effects of methamphetamine. However, co-administration of MS-377 attenuated the development of methamphetamine-induced behavioral sensitization in a dose-dependent manner. These results suggested that sigma(1) receptors play an important role in the developmental period of behavioral sensitization induced by methamphetamine in rats.
Takahashi
S
S
Medicinal Research Department, Institute of Biological Science, Mitsui Pharmaceuticals Inc., 1900-1 Togo, Mobara-shi, 297-0017, Chiba, Japan. shinji_takahashi@mitsui-pharm.co.jp
Miwa
T
T
Horikomi
K
K
D000284:Administration, Oral; D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006220:Haloperidol / Q000008:administration & dosage; D007274:Injections, Intraperitoneal; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage*; D010879:Piperazines / Q000008:administration & dosage; D011759:Pyrrolidines / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D017480:Receptors, sigma / Q000502:physiology*; D012559:Schizophrenia / Q000188:drug therapy; D013239:Stereotyped Behavior / Q000187:drug effects / Q000502:physiology; D013644:Tartrates; D000097605:Sigma-1 Receptor
D014150:Antipsychotic Agents; D006220:Haloperidol; D008694:Methamphetamine; D010879:Piperazines; D011759:Pyrrolidines; D017480:Receptors, sigma; D013644:Tartrates; D000097605:Sigma-1 Receptor; C464615:1-(4-chlorophenyl)-3-(4-(2-methoxyethyl) piperazin-1-yl)methyl-2-pyrrolidinone tartrate