Related Experiment Videos
Involvement of sigma 1 receptors in methamphetamine-induced behavioral sensitization in rats
S Takahashi1, T Miwa, K Horikomi
1Medicinal Research Department, Institute of Biological Science, Mitsui Pharmaceuticals Inc., 1900-1 Togo, Mobara-shi, 297-0017, Chiba, Japan. shinji_takahashi@mitsui-pharm.co.jp
Abstract:
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.
Insights
MS-377, a selective sigma(1) ligand, reduced methamphetamine-induced behavioral sensitization in rats. This suggests sigma(1) receptors are key in developing this sensitization, offering potential therapeutic insights for schizophrenia treatment.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Schizophrenia treatment remains a challenge, necessitating novel therapeutic targets.
- Methamphetamine-induced behavioral sensitization is a relevant preclinical model for studying addiction and psychosis.
Purpose of the Study:
- To investigate the effect of MS-377, a selective sigma(1) ligand, on methamphetamine-induced behavioral sensitization in a rat model.
- To explore the role of sigma(1) receptors in the development of behavioral sensitization.
Main Methods:
- Rats were administered methamphetamine (2 mg/kg) daily for 10 days to induce behavioral sensitization.
- MS-377 (1.875-15 mg/kg) was co-administered with methamphetamine.
- Stereotypy and behavioral sensitization were assessed.
Main Results:
- Methamphetamine administration led to enhanced stereotypy and behavioral sensitization.
- MS-377 did not alter the acute effects of methamphetamine.
- Co-administration of MS-377 dose-dependently attenuated the development of methamphetamine-induced behavioral sensitization.
Conclusions:
- Sigma(1) receptors play a significant role in the developmental phase of methamphetamine-induced behavioral sensitization.
- MS-377 demonstrates potential as a therapeutic agent by modulating sigma(1) receptor activity.
- These findings support further investigation of sigma(1) ligands for schizophrenia treatment.