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Inhibition of mouse-killing behavior by S-adenosyl-L-methionine in midbrain raphe-lesioned and
T Yamamoto1, S Yatsugi, M Ohno
1Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Abstract:
The effect of S-adenosyl-L-methionine (SAM), a methyl donor, on mouse-killing behavior in rats with lesions of the midbrain raphe nuclei and in olfactory-bulbectomized rats was investigated. Systemic administration of SAM at doses of 180 and 320 mg/kg IP caused a significant inhibition of both kinds of mouse-killing behavior. The inhibitory effects of SAM on both types of mouse-killing behavior were almost equipotent. Microinjection of SAM at 10-100 micrograms/rat into the lateral ventricle also inhibited mouse-killing behavior induced by raphe lesions in a dose-dependent manner. The ED50 value of SAM for this effect was 38.6 (18.4-81.4) micrograms/rat. It is concluded that SAM has inhibitory effects on mouse-killing behavior in both raphe-lesioned and olfactory-bulbectomized rats through a site of action in the central nervous system.
Insights
S-adenosyl-L-methionine (SAM) significantly reduces mouse-killing behavior in rats. This methyl donor acts centrally to inhibit aggression in both raphe-lesioned and olfactory-bulbectomized models.
Area of Science:
- Neuroscience
- Pharmacology
- Behavioral Science
Background:
- Mouse-killing behavior is a complex predatory aggression observed in rodents.
- Midbrain raphe nuclei lesions and olfactory bulbectomy are known to induce this behavior.
- S-adenosyl-L-methionine (SAM) is an endogenous methyl donor with potential neuromodulatory roles.
Purpose of the Study:
- To investigate the effect of S-adenosyl-L-methionine (SAM) on mouse-killing behavior in established rat models.
- To determine if SAM exerts its effects systemically or centrally.
Main Methods:
- Systemic administration of SAM (180 and 320 mg/kg IP) in olfactory-bulbectomized rats and rats with midbrain raphe nuclei lesions.
- Intracerebroventricular microinjection of SAM (10-100 micrograms/rat) into the lateral ventricle of raphe-lesioned rats.
- Dose-response analysis and ED50 calculation for central administration.
Main Results:
- Systemic SAM administration significantly inhibited mouse-killing behavior in both rat models.
- The inhibitory effects of systemic SAM were found to be equipotent across both experimental conditions.
- Intracerebroventricular SAM microinjection dose-dependently inhibited mouse-killing behavior in raphe-lesioned rats, with an ED50 of 38.6 micrograms/rat.
Conclusions:
- S-adenosyl-L-methionine (SAM) possesses significant inhibitory effects on mouse-killing behavior.
- These inhibitory effects are mediated through a central nervous system site of action.
- SAM may represent a potential therapeutic agent for aggression-related disorders.