Pharmacological modification of shock potentiated amphetamine lethality

The ability of the acute application of inescapable footshock to potentiate d- and d,l-amphetamine in rodents has previously been ascertained. The present study confirmed these results and demonstrated a similar interaction with l-amphetamine. Aggregation further enhanced this potentiation. Prior subacute exposure to shock did not prevent the potentiated lethality. Shock potentiated amphetamine lethality was antagonized by pretreatment with agents which indirectly reduce catecholamine release (6-hydroxydopamine, α-methyl-p-tyrosine) and by bilateral adrenalectomy. However antagonism did not result from pretreatment with the adrenergic blocking agents propanolol and phenoxybenzamine. Pretreatment with methoxamine and hydrocortisone likewise did not afford protection. However pretreatment with haloperidol and pentobarbital completely antagonized the potentiated lethality whereas morphine and fenfluramine pretreatment did not provide protection. Shock potentiated amphetamine lethality was enhanced by pretreatment with physostigmine and neostigmine but was antagonized by pretreatment with methylatropine. However atropine pretreatment enhanced lethality. It would appear that the release of norepinephrine from the brain and/or the adrenal medulla either is directly involved in mediating amphetamine lethality or in mediating the effects of acute stress on emphetamine's lethal actions.