[Chronic prenatal exposure to diazepam, brain metabolism and behavior: long-term consequences in the adult rat].
The long-term consequences of a neonatal exposure to diazepam (DZP) on behavioral abilities and local cerebral metabolic rates for glucose (LCMRglc) in selected brain regions involved in the control of memory and anxiety were studied in adult rats. Rat pups received a daily subcutaneous injection of 10 mg/kg DZP or of the dissolution vehicle from postnatal day (P) 2 to 21. Learning and memory were tested in P60-P70 rats on 5 consecutive days in a T maze and an eight arm maze while anxiety and reaction to novelty were tested in a 2 compartment box with a 2 step staircase on one side. Social behavior was evaluated in a condition of restricted access to food. LCMRglcs were measured at P60 by the quantitative autoradiographic [14C]deoxyglucose method. In the T maze, when performed without delay between the 2 trials, the rate of alternation was significantly lower in DZP than in vehicle-exposed rats on the first 2 days of testing and similar in both groups on days 3-5. In the procedure with a 30 s intertrial delay, the rate of alternation was similar in DZP and vehicle-treated rats on all days of testing. In the eight arm maze, DZP-treated rats were more active, i.e. entering more arms per min than control animals. The number of arms entered before the first error was lower on day 1 and higher on day 3 in DZP compared to vehicle-exposed rats. In the 2 compartment box, DZP-treated rats crossed more often the lower step of the staircase and spent more time than controls on the 2 steps of the staircase while control rats made more rearings than DZP-exposed rats in the well protected corner of the box. LCMRglcs were decreased by early DZP exposure in several cortical regions, mammillary body, septum and dorsomedian caudate nucleus. In conclusion, an early chronic DZP treatment induces an increase in activity, only a delay but no impairment in learning and leads to a decrease in the level of anxiety and emotionality leading to an active response to novelty. These quite subtle behavioral changes are accompanied by discrete metabolic changes and probably reflect the state of hyperactivity/hyperarousal of these animals which could result from a change in the distribution, the sensitivity and/or function of GABA-BZD receptors.
Schroeder
H
H
INSERM U272, Université Henri Poincaré, Nancy.
Toniolo
A M
AM
Desor
D
D
Nehlig
A
A
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001143:Arousal / Q000187:drug effects*; D001786:Blood Glucose / Q000378:metabolism; D001921:Brain / Q000187:drug effects*; D001931:Brain Mapping; D003975:Diazepam / Q000494:pharmacology*; D004644:Emotions / Q000187:drug effects*; D004734:Energy Metabolism / Q000187:drug effects*; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011340:Problem Solving / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D014151:Anti-Anxiety Agents; D001786:Blood Glucose; D003975:Diazepam