title: Reproductive experience reduces the sedative, but not anxiolytic effects of diazepam.
abstract: Benzodiazepines are frequently prescribed to women for both their anxiolytic and hypnotic effects. Previous studies in rodents have demonstrated reproductive experience, i.e. pregnancy and lactation, can alter sensitivity to certain drugs, such as morphine. The purpose of the present study was to determine whether reproductive experience alters sensitivity to the benzodiazepine, diazepam. Two groups of subjects were generated, a primparous group (pregnancy+21 days of lactation) and an age-matched, nulliparous group. All subjects were injected with diazepam (0.0, 0.5, 2.0 or 2.5 mg/kg) at least 6 weeks after primiparous females weaned their litters. Twenty minutes post-injection, subjects were place in an activity chamber and locomotor behavior was measured. Thirty minutes post-injection, subjects were tested on an automated elevated plus maze. In addition to behavioral testing, diazepam's effects on corticosterone levels were measured. Overall, diazepam's sedative effects on locomotor activity were significantly reduced in primiparous females when compared to nulliparous controls as determined both in the activity chamber and on the elevated plus maze. There was, however, no significant effect of reproductive experience on the anxiolytic effects of diazepam in the elevated plus maze. Finally, while diazepam increased corticosterone in both groups, primiparous females were less sensitive to the effects of the drug on corticosterone secretion. These results indicate that the effects of diazepam on locomotor activity and corticosterone secretion are attenuated following reproductive experience.
authors.affiliation: Department of Biomedical Sciences, Tufts University, Cummings School of Veterinary Medicine, North Grafton, MA 01536, USA. elizabeth.byrnes@tufts.edu
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Byrnes
authors.forename: Robert S
authors.initials: RS
authors.lastname: Bridges
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001831:Body Temperature / Q000187:drug effects; D003345:Corticosterone / Q000378:metabolism; D003975:Diazepam / Q000494:pharmacology*; D030762:Estrous Cycle / Q000502:physiology; D005260:Female; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D010298:Parity / Q000502:physiology; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000502:physiology*; D013315:Stress, Psychological / Q000503:physiopathology / Q000523:psychology
chemical_list: D014151:Anti-Anxiety Agents; D006993:Hypnotics and Sedatives; D003975:Diazepam; D003345:Corticosterone