RESERPINE-INDUCED ALTERATIONS IN BRAIN AMINES AND THEIR RELATIONSHIP TO CHANGES IN THE INCIDENCE OF MINIMAL ELECTROSHOCK SEIZURES IN MICE

¹ Department of Pharmacology, West Virginia University Medical Center, Morgantown, West Virginia

The injection of a single dose of reserpine to mice leads to a reduction in the threshold for minimal electroshock seizures (MES). This change was accompanied by a decline in brain concentrations of norepinephrine, dopamine and serotonin (5-HT). The return of the incidence of seizures to normal, however, was not accompanied by an equivalent return of brain amine concentrations towards control levels. The administration of an inhibitor of synthesis of either the catecholamines (H44/68) or of 5-HT (H69/17) with reserpine prolonged, but did not prevent, the eventual return of the MES threshold to normal. The administration of both inhibitors to reserpine-treated animals, however, was effective in preventing the MES threshold from returning to control levels. If either synthesis inhibitor was given alone to nonreserpine-treated animals, no increase in seizure activity occurred despite the fact that depletion of the appropriate amine was produced. A reduction in the MES threshold in untreated animals was only produced when both catecholamine and 5-HT synthesis were simultaneously inhibited. The administration of precursors of catecholamines and 5-HT to reserpine-treated mice resulted in an antagonism of reserpine's effect on minimal electroshock seizures and an elevation of brain amine levels. It is concluded from these studies that brain amines are intimately involved in the effects of reserpine on MES threshold. It is suggested that the recovery of the MES threshold, after reserpine administration, may more closely parallel the return of the ability of the central nervous system nerve granules to accumulate biogenie amines than to total brain amine levels. Our studies suggest that both the catecholamines and 5-HT are involved in the control of the MES threshold.