Ethopharmacology of maternal aggression in mice: effects of diazepam and SM-3997.
The present study investigated whether there is any difference between the effects of benzodiazepine and non-benzodiazepine anxiolytics on maternal aggression in lactating mice, using an ethological technique. We used SM-3997, a 5-HT1A receptor ligand, as a non-benzodiazepine anxiolytic. Behavior towards an intruder male mouse was assessed on postpartum days 5 and 7 in female mice that had been housed alone since the end of the 4-day mating period. Acute oral administration of diazepam had a biphasic effect on the frequency of bites: 1 mg/kg diazepam significantly increased bite frequency, while 2.5 mg/kg diazepam significantly decreased it. However, 2.5 mg/kg diazepam also caused a significant decrease in locomotor activity. In contrast, SM-3997 (1, 2.5 and 5 mg/kg p.o.) significantly decreased the frequency of bites in a dose-dependent manner without causing motor dysfunction. Chronic treatment with 5 mg/kg SM-3997 significantly decreased the frequency of bites when compared with vehicle, whereas diazepam was ineffective at the doses used (0.5 and 1 mg/kg p.o.). The findings suggest that the proaggressive effect is specific to benzodiazepines, and that 5-HT1A receptors may be involved in the suppression of maternal aggression in mice.
Department of Pharmacology, Ehime University School of Medicine, Japan.
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Yoshimura
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Ogawa
D000374:Aggression / Q000187:drug effects*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D003975:Diazepam / Q000494:pharmacology*; D005260:Female; D054833:Isoindoles; D008297:Male; D008425:Maternal Behavior; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*
D014151:Anti-Anxiety Agents; D054833:Isoindoles; D010879:Piperazines; D011743:Pyrimidines; C055267:tandospirone; D003975:Diazepam