LONG-TERM CONSEQUENCES OF NEONATAL EXPOSURE TO DIAZEPAM ON CEREBRAL GLUCOSE-UTILIZATION, LEARNING, MEMORY AND ANXIETY

The long-term consequences of neonatal exposure to diazepam (DZP) on b ehavioral abilities and local cerebral glucose utilization (LCGU) in 1 2 brain regions involved in the control of memory and anxiety were stu died in adult rats. Rat pups received a daily subcutaneous injection o f 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 over 5 consecut ive days in a T maze and an eight-arm maze while anxiety and reaction to novelty were tested in a two-compartment box with a two-step stairc ase on the enriched side. LCGU was measured in the P60 rat by the quan titative autoradiographic [C-14]deoxyglucose method, In the T maze, wh en performed without delay between the two trials, the rate of alterna tion was significantly lower in DZP- than In vehicle-exposed rats on t he first 2 days of testing and similar in both groups on days 3-5. In the procedure with a 30 a intertrial delay, the rate of alternation wa s 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., entered m ore arms per minute than control animals. The number of arms entered b efore the first error was lower on day 1 and higher on day 3 in DZP- c ompared to vehicle-exposed rats. In the two-compartment box, DZP-treat ed rats crossed more often and spent more time than controls on the lo wer step of the staircase while control rats made more rearings and sp ent more time than DZP-exposed rats in the well protected corner of th e box. LCGU were decreased by early DZP exposure in six regions which were mammillary body, septum, visual and prefrontal cortices, dorsomed ian caudate nucleus and mediodorsal thalamus. In conclusion, postnatal DZP treatment induced at adulthood an increase in activity, a delay i n task acquisition but no learning-memory impairment and reduced the l evel of anxiety allowing active responding to novelty. These quite sub tle behavioral changes were accompanied by discrete metabolic decrease s in regions mediating anxiety, reflecting a change in the level of an xiety and emotionality. (C) 1997 Elsevier Science B.V.