SHORT-TERM AND LONG-TERM EFFECTS OF NEONATAL DIAZEPAM EXPOSURE ON LOCAL CEREBRAL GLUCOSE-UTILIZATION IN THE RAT

The short- and long-term consequences of a neonatal exposure to diazep am (DZP) on the postnatal changes in local cerebral metabolic rates fo r glucose (LCMRglcs) were studied by the quantitative autoradiographic [C-14]2-deoxyglucose method in a total number of 66 brain structures of freely moving rats. Rat pups received a daily subcutaneous injectio n of 10 mg/kg DZP, of the dissolution vehicle or of saline from postna tal day 2 (P2) to 21 (P21). The animals were studied at 4 ages, P10, P 14, P21 and P60. DZP induced a decrease in LCMRglcs which was restrict ed to 13 areas at P10, mainly sensory and limbic regions. At P14, the treatment had significant metabolic effects on 48 structures belonging to all functional systems. By P21, 23 brain areas were still affected by the treatment, mainly sensory, limbic and motor areas: At P60, i.e . at about 40 days after the end of drug exposure, LCMRglcs still decr eased in 14 brain regions which were mainly sensory and limbic structu res. The structures most sensitive to both short- and long-term conseq uences of the anticonvulsant treatment are mammillary body, limbic cor tices and sensory regions. The dissolution vehicle increased LCMRglcs in a few brain regions at P14 and P60, whereas it decreased metabolic levels in 5 brain regions at P21. The results of the present study sho w that the brain appears to be particularly vulnerable to the treatmen t at P14, period of active brain growth, whereas by P21, the drug is m ore actively metabolized and a tolerance to the treatment may occur. T he long-term effects of the treatment are in good accordance with the well-known effects of DZP on anxiety, sedation and memory. The structu res most sensitive to early neonatal DZP exposure are the mammillary b ody, limbic cortices and sensory regions that all contain a high densi ty of benzodiazepine binding sites.