Antagonism of reserpine behavioral depression by d-amphetamine

increased sensitivity of peripheral autonomic effectors in reserpine-treated animals. While re-sponses to norepinephrine and other “direct-acting ” amines were exaggerated, the activity of amphetamine and other indirect-acting amines was diminished 24 to 48 hours after reserpine was administered. These authors sug-gested an inverse relationship between the sensitivity of adrenergic receptors and the quantity of transmitter substance at adrenergic nerve terminals. On the other hand, Fleming and Trendelenburg (1961) demonstrated that marked depletion of catecholamines from the nictitating membrane by reserpine took place well before the onset of altered sensitivity to norepinephrine. Based on this and similar evidence, Trendelenburg and Weiner (1962) and Kirpekar et al. (1962) concluded that reserpine enhances the sensitivity of adrenergic receptors by a prolonged failure of transmission at the neuroeffector junction. Increased excitatory effects of sympathomi-metic amines on the central nervous system of reserpine-pretreated animals have been demon-strated also (Smith, 1963; Quinton and Halli-well, 1963). In these studies, however, d-am-phetamine’s activity was much enhanced in animals pretreated with reserpine 24 hours pre-viously. Smith, who measured spontaneous loco-motor activity as an index of central nervous system excitability, proposed that d-ampheta-mine stimulates directly certain adrenergic re-ceptors in the brain. Both reserpine and d-amphetamine have prominent effects on conditioned avoidance be-havior. The study of their interactions on these responses might assist in explaining their effects on central nervous functions. In the present Received for publication May 4, 1964