BEHAVIORAL AND METABOLIC CONSEQUENCES OF NEONATAL EXPOSURE TO DIAZEPAM IN RAT PUPS

The short-term consequences of a neonatal exposure to diazepam (DZP) o n neurobehavioral development and postnatal changes in local cerebral metabolic rates for glucose (LCMRglcs) in selected regions were studie d in rats. Rat pups received a daily subcutaneous injection of 10 mg/k g DZP or of the dissolution vehicle from Postnatal Day 2 (P2) to 21 (P 21). DZP did not affect the static righting reflex tested at P4 but in creased suspension time at P10 and time to complete a 180 degrees pivo ting on an inclined plane at P9. In a locomotor coordination test perf ormed at P20, swimming or climbing on a vertical pole was not affected by DZP while the drug impaired the ability of the rat to place its hi ndpaws on the horizontal platform after climbing. Likewise, DZP induce d marked decreases (19-45%) in LCMRglcs in most structures studied at P10, P14, and P21. The results of the present study show that neonatal DZP treatment induces motor deficits that appear to be quite subtle, to concern mainly posture and body balance. They are not apparent in t asks such as swimming or climbing but become obvious in more difficult tasks such as achieving a horizontal quadruped position on a platform after a climbing phase. Decreases in cerebral energy metabolism appea r to be mainly located in areas controlling posture and body balance a nd are partly correlated with the locomotor impairments recorded in th e present study. (C) 1995 Academic Press, Inc.