Male olfactory cues affect mothers' behavior in mice: effects of benzodiazepines

Rationale: Threatening social stimuli were used in this study as aversive conditions to test anxiety in lactating female mice. The odors of potential infanticidal males or the "stress odor" left by restrained mice represented two aversive conditions that have been suggested to modulate the time spent by the mothers to reach their pups after 30 min of separation. Objectives: The effects of drugs acting at the benzodiazepine receptors were evaluated on the behavior of mothers exposed to different threatening social cues. Methods: Lactating mice of the NMRI outbred strain with 8-day old pups were treated with (1) chlordiazepoxide (CDP) 2.5, 5.0 and 10 mg/kg i.p.; (2) flumazenil 10 mg/kg i.p. and (3) methyl ?-carboline-3-carboxylate (?-CCM) 3.0 mg/kg i.p. Results: The odors left by stressed females changed the mothers' exploratory behavior, but not the latency to reach pups. The latency was higher in the presence of cues from potentially infanticidal males. CDP (5.0 mg/kg) reduced the time spent to contact pups, whereas the other CDP doses did not modify the dam's behavior. Flumazenil, given in combination with CDP (5.0 mg/kg) antagonized the latter anxiolytic effect. In addition, in the presence of cues from potentially infanticidal males ?-CCM had anxiogenic activity, increasing latency to reach pups. The same CDP and ?-CCM doses were ineffective in the presence of cues from stressed females and in the absence of olfactory cues from conspecifics. Conclusions: This study provides behavioral and pharmacological validation of a new model of anxiety specifically designed for lactating females.