NEONATAL MONOSODIUM GLUTAMATE TREATMENT ALTERS BOTH THE ACTIVITY AND THE SENSITIVITY OF THE RAT HYPOTHALAMO-PITUITARY-ADRENOCORTICAL AXIS

We have investigated the effects of monosodium glutamate (MSG) lesioni ng of the arcuate nucleus on both central and peripheral components of the hypothalamo-pituitary-adrenocortical (HPA) axis under basal condi tions and under acute and chronic stress. Plasma ACTH levels were lowe r in MSG-lesioned rats (27 +/- 7 pg/ml) compared with controls (71 +/- 18 pg/ml) while corticosterone levels were elevated (523 +/- 84 ng/ml compared with 176 +/- 34 ng/ml). Quantititative in situ hybridization histochemistry revealed that corticotrophin-releasing factor mRNA lev els in the medial parvocellular part of the hypothalamic paraventricul ar nucleus were significantly lower in MSG-treated rats. MSG lesioning resulted in an enhanced response of corticosterone to restraint stres s (1309 +/- 92 ng/ml compared with 628 +/- 125 ng/ml in sham-lesioned animals), while ACTH responses to restraint stress in MSG-lesioned and sham-MSG groups were not significantly different (160 +/- 24 pg/ml an d 167 +/- 24 pg/ml respectively). These data suggest that MSG-lesioned rats have an increased adrenocortical sensitivity. In rats subjected to the chronic osmotic stimulus of drinking 2% saline for 12 days, pla sma ACTH levels were significantly reduced (15 +/- 5 pg/ml) and the AC TH and corticosterone responses to restraint stress were eliminated. A CTH levels were also reduced in MSG-treated animals given 2% saline an d the ACTH response to acute stress remained absent in these animals. However, a robust corticosterone response to restraint stress was obse rved in saline-treated MSG-lesioned rats. These data demonstrate that MSG lesioning results in elevated basal and stress-induced plasma cort icosterone, and restores the adrenocortical response to stress which i s absent in chronically osmotically stimulated rats. The evidence is c onsistent with the suggestion that MSG lesions a pathway involved in t onic inhibition of the HPA axis. In addition, the adrenocortical sensi tivity to ACTH and other secretagogues may be increased in MSG-treated animals.