Trans-synaptic induction of adrenal tyrosine hydroxylase following amphetamine treatment in the rat

Abstract

Daily injections of d-amphetamine sulfate (5 mg/kg), given in combination with the hepatic microsomal inhibitor iprindole, increased the tyrosine hydroxylase activity in rat adrenals by 41% after 4 days. Choline acetyl-transferase activity also increased significantly. Neither change was observed in animals whose adrenals had been denervated (by transection of the splanchic nerve), thus indicating that the increases were mediated by the central nervous system and by trans-synaptic mechanisms. The chronic administration of methamphetamine increases tyrosine hydroxylase activity in the adrenal glands of the chicken (MANDELL and MORGAN, 1970) and the rat (BUENING and GIBB, 1974). BREESE, COOPER and MUELLER (1974) hove noted similar increases in adrenal tyrosine hydroxylase activity in animals receiving 5 mg/kg of d-amphetamine twice daily for 3 days. The mechanisms by which amphet-amines modify adrenal tyrosine hydroxylase activity could involve direct actions on chromaffin cells (e.g., to release catecholamine molecules, thereby activating feedback mechanisms coupled to the enzyme), or central actions (to activate the flow of impulses along the preganglionic cholinergic nerves innervating the adrenal, thereby increasing enzyme activity via trans-synaptic mechanisms (COSTA, GUIDOTTI and HANBAUER, 1974). To explore the latter possibility, the extent to which treatment with d-amphetamine changes tyrosine hydroxylase activity in adrenals previously subjected to surgical denervation was determined.