PHARMACOLOGICAL EVIDENCE FOR INVOLVEMENT OF GABA-ERGIC SYSTEM IN LOCOMOTOR STIMULATION PRODUCED IN MICE BY 1,3-DIMETHYL-5-AMINOADAMANTANE (D-145)

Both 1.3-dimethyl-5-aminoadamantane (D-145) and d-amphetamine produced locomotor stimulation in mice. Pimozide was more effective in blocking the effect of d-amphetamine than that of D-145. Reserpine treatment blocked the D-145-induced stimulation, but did not modify the effect of d-amphetamine. The influence of α-methyl-p-tyrosine was opposite to that of reserpine. Phenoxybenzamine did not significantly modify the response of either of these stimulants. It was concluded that both these drugs preferentially stimulate the dopaminergic areas of brain, and that D-145 acts by releasing the granular stores of dopamine. In mice pretreated with either aminooxyacetic acid or lioresal, D-145 failed to produce locomotor stimulation, but such pretreatments did not modify the response to d-amphetamine. It seems that D-145 acts as a GABA antagonist and that the removal of the inhibitory effect of the GABA system over the dopaminergic pathways by D-145 results in the activation of the latter, leading to locomotor stimulation. The d-amphetamine-induced stimulation does not involve the GABA system. 1,3-Dimethyl-5-aminoadamantane is the first locomotor stimulant drug that seems to act primarily via the GABA system. © 1978.