Sexual segregation in infancy and bi-directional benzodiazepine effects on hot-plate response and neophobia in adult mice.
In the present experiment, the hypothesis that rearing animals in conditions of sexual segregation in infancy (ISS) would affect their adult behavioral reactivity to drug or environmental challenges was tested. Outbred Swiss CD-1 mouse litters were reduced at birth to six pups according to three conditions: MM (all males), MF (sex-balanced composition), and FF (all females). At weaning (day 21), all mice were rehoused in unisexual groups. At adulthood (day 70), animals were challenged either with BDZ agonist chlordiazepoxide (CDP at 2.5- or 5.0-mg/kg dose) or BDZ receptor partial inverse agonist Ro 15-3505 (RO at 3-, 10-, or 30-mg/kg dose) and assessed in sequence for pain reactivity in a hot-plate apparatus (set at 55 +/- 1 degrees C), for locomotor activity in a Varimex apparatus, and finally for neophobia level by measuring the latency to first approach a novel object. As concerns the hot-plate test, lick latency was significantly shortened in MF females receiving CDP (5.0 mg/kg), while RO was either ineffective in MF females or induced a prominent dose-dependent analgesia in FF females. Activity was decreased by CDP (2.5 mg/kg) and enhanced by RO (3.0 mg/kg). For latency to approach a novel object, males as a whole exhibited shorter times than females. Mixed-sex animals of both sexes were less fearful, being also more explorative than their corresponding unisexually reared groups. In particular, MF males receiving either a 5.0-mg/kg CDP dose or a 3.0-mg/kg RO dose explored the object more often than MM males.(ABSTRACT TRUNCATED AT 250 WORDS)
Laviola
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Section of Behavioral Pathophysiology, Istituto Superiore di Sanità, Rome, Italy.
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D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn / Q000523:psychology*; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001007:Anxiety / Q000523:psychology*; D001569:Benzodiazepines; D004777:Environment; D005260:Female; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010147:Pain Measurement; D011963:Receptors, GABA-A / Q000187:drug effects; D012737:Sex Factors
D000700:Analgesics; D014151:Anti-Anxiety Agents; D011963:Receptors, GABA-A; D001569:Benzodiazepines