Perinatal upregulation of benzodiazepine receptor ontogenesis: "fearless" and more efficient goal-directed behavior of adult rat progenies.
Pregnant and subsequently lactating rats had ad lib access to drinking water which contained either a benzodiazepine antagonist, Ro 15-1788 or diazepam (DZ). On the average, the rats consumed 2.9 mg/kg/day of Ro 15-1788 or 5.3 mg/kg/day of diazepam over the time period of 3 weeks, from gestation day 14 through postpartum day 14. The control group consumed equivalent volumes of the drug vehicle in water. While Ro 15-1788 had no apparent toxic effects, the numbers of viable pups in the DZ group were significantly reduced. The mean weight of the viable pups, and their gross behavior were not different in all three groups. However, the fully mature 4.5-month-old male progenies exposed to Ro 15-1788 were much more efficient in the radial arm maze test than the control or the diazepam-exposed animals; they rapidly habituated to the novel environment, their exploratory activity was uninhibited by distracting visual and auditory stimuli, they made fewer "working memory" errors in collecting baits, had a much better control over their emotional responses and the autonomic nervous system, as shown by very low defecation/urination scores, and, at the age of 5 months, they had a significant (66%) increase in the density of benzodiazepine receptors in the hippocampal formation, as compared to the control or the diazepam-exposed progenies. In conclusion, the upregulation of benzodiazepine receptor ontogenesis is retained in adult animals and resulted in improved "working memory" and better control over emotional responses that were particularly evident when the animals were challenged by novel and "intimidating" environmental stimuli.
Marczynski
T J
TJ
Department of Pharmacology, University of Illinois at the Medical Center, Chicago 60612.
Hawkins
M C
MC
Swann
P G
PG
Krivograd
A F
AF
Patel
M K
MK
Dugich
M
M
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003975:Diazepam / Q000633:toxicity; D004326:Drinking / Q000187:drug effects; D005239:Fear / Q000187:drug effects*; D005260:Female; D005442:Flumazenil / Q000494:pharmacology; D005445:Flunitrazepam / Q000378:metabolism; D007858:Learning / Q000187:drug effects; D009949:Orientation / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects*
D011963:Receptors, GABA-A; D005442:Flumazenil; D005445:Flunitrazepam; D003975:Diazepam