The objective of this study is to determine the mechanism of action of amphetamine, dextroamphetamine, methamphetamine and other central nervous system (CNS) stimulants on single identified nerve cells. Preliminary observations indicate that dextroamphetamine can act as a cholinomimetic agent on cholinoceptive cells or as a sympathomimetic agent on dopaminoceptive cells of the snail brain. Intracellular recordings will be made from cholinergic and dopaminergic cells of the brain of the snail, Helix pomatia. Drug effect will be assessed on the basis of effect on membrane potential, action potential contour, membrane resistance, changes in ionic permeability and changes in the frequency of initiation of action potentials. Cholinergic mechanism will be distinguished from adrenergic mechanism by use of the appropriate blocking agents: cholinergic (d-tubocurarine, atropine), adrenergic (dihydroergotamine, MJ 1999) and neuronal (reserpine, guanethidine, alpha-methyltyrosine). These data will suggest whether or not the mechanism of action of amphetamine on nerve cells is analagous with known effects of amphetamine on tissues other than the brain. This is presently not known. A second objective is to study the process by which tolerance develops to the excitatory action of the central nervous system stimulants. This phase will involve a comparison of amphetamine- induced tolerance to the desensitization of these cells induced by nicotine.
NIH ExPorter
NIH ExPorter