Inhibition of the uptake of tritiated catecholamines by antidepressant and related agents

Behavioural studies of the actions of cocaine, monoamine oxidase inhibitors and iminodibenzyl compounds on central dopamine neurones

“…That this turning is abolished by the tyrosine hydroxylase inhibitor a-methyl-p-tyrosine, is consistent with the hypothesis that turning reflects increased release of cerebral catecholamine stores. However, neither administration of cocaine, which blocks the neuronal mechanism for dopamine uptake (Ross & Renyi, 1967) nor of a MAO inhibitor, which increases cerebral monoamine concentrations (Everett & Wiegand, 1962), separately, will cause turning behaviour. A possible interpretation of the interaction therefore is that turning occurs only when there is an increase in cerebral dopamine concentration combined with inhibition of the neuronal uptake process.…”

“…There are several possible modes of interaction between the amphetamines and dopamine-containing neurones-(i) blockade of dopamine uptake (Ross & Renyi, 1967); (ii) MAO inhibition (Blaschko, Richter & Schlossmann, 1937;Glowinski, 1970), and (iii) release of dopamine from nerve terminals (Carlsson, 1970;. Since neither cocaine alone, nor nialamide or pargyline alonecauses turning, it seems unlikely that the action of the amphetamines is mediated solely by either mechanism (i) or (ii).…”

“…uptake blockade and MAO inhibition). However, the amphetamines are weak inhibitors of the dopamine uptake process by comparison with cocaine (Ross & Renyi, 1967). Moreover, reserpine (5 mg/kg) given 24 h previously greatly diminishes the action of the cocaine-MAO inhibitor combination but potentiates that of (+)-amphetamine.…”

“…Desipramine inhibits noradrenaline uptake into cortical slices at a concentration of 3 x 10-8M, but inhibits uptake of dopamine into striatal slices only at a concentration of 5X10-5M. Cocaine, however, inhibits cortical noradrenaline uptake at a concentration of 1 x 10-6M and striatal dopamine uptake at the similar concentration of 2x 10-6M (Ross & Renyi, 1967). Thus the relative desipramine: cocaine potencies are 33: 1 in blocking noradrenaline uptake, and 1: 25 in blocking dopamine uptake.…”

“…Experiments on the inhibition of uptake of tritiated catecholamines into cortical and striatal slices (Ross & Renyi, 1967;Fuxe, Hamberger & Malmfors, 1967) suggest that there are differences between the neuronal uptake mechanisms for noradrenaline and for dopamine. Desipramine inhibits noradrenaline uptake into cortical slices at a concentration of 3 x 10-8M, but inhibits uptake of dopamine into striatal slices only at a concentration of 5X10-5M.…”