Prenatal oxazepam enhances mouse maternal aggression in the offspring, without modifying acute chlordiazepoxide effects.
In the rat, behavioral changes during lactation are in several ways similar to those produced by benzodiazepines (BDZ). Moreover, an increased activity at the GABA/BDZ receptor complex has been found in both conditions. We tested the hypothesis that early manipulation of this neurochemical system by prenatal BDZ exposure should affect typical responses of lactating dams, such as maternal aggression. Outbred CD-1 mice were treated with either oxazepam (15 mg/kg PO twice/day on days 12-16 of fetal life) or vehicle and fostered at birth to untreated dams. Female offspring were subsequently mated at the young-adult stage and used to assess maternal aggressive responses towards a male intruder. In a first 5-min test on postpartum day 6, the prenatal oxazepam animals showed a reduced Latency to the First Attack, a markedly enhanced frequency of several offensive scores (such as Fighting Episodes, Attacks, and Offensive Upright, On Top, and Kicking Postures), a decrease of Submissive Postures and a reduced duration of time spent lying still (Out of the Nest). The tests were repeated 48 h later after IP treatment by either chlordiazepoxide (10 mg/kg) or saline. The drug significantly enhanced locomotor activity as well as the frequency of Fighting Episodes and of Attacks, while decreasing the number of Submissive Postures and the time spent On Nest. These effects were not significantly modified by prenatal oxazepam exposure. This suggests that long-term and acute effects of benzodiazepines are produced either by changes in different regulatory systems or by different types of changes in the same system.
Laviola
G
G
Section of Behavioural Pathophysiology, Istituto Superiore di Sanità, Roma, Italy.
de Acetis
L
L
Bignami
G
G
Alleva
E
E
D000374:Aggression / Q000187:drug effects*; D000818:Animals; D002707:Chlordiazepoxide / Q000008:administration & dosage / Q000633:toxicity*; D004357:Drug Synergism; D005260:Female; D007774:Lactation; D008431:Maternal-Fetal Exchange; D051379:Mice; D010076:Oxazepam / Q000008:administration & dosage / Q000633:toxicity*; D011247:Pregnancy; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology
D011963:Receptors, GABA-A; D010076:Oxazepam; D002707:Chlordiazepoxide