Tremorogenic effects of intracaudate d-amphetamine and their suppression by dopamine

Pronounced tremors were produced in unanesthetized cats following intracaudate (I.C.) injections of either d-amphetamine (15 mug), dl-methamphetamine (20 mug), l-amphetamine (48 mug) or 3-methoxytyramine (68-120 mug). Yet, a series of other chemically and pharmacologically related phenylethylamines, including dopamine (90 mug), were not tremorogenic even at substantially higher doses. The d-amphetamine tremors developed rapidly, failed to exhibit tachyphylaxis to repeated challenging doses (15 mug) and were not influenced by pretreatment with alpha-methyl-p-tyrosine. They also developed independently of local acetylcholine activity as evidenced by the inability of cholinergic antagonists (scopolamine and hemicholinium) to interfere with the tremors. Significant qualitative differences were found between the I.C. effects of d-amphetamine (15 mug) and dopamine (15-90 mug): d-amphetamine further increased the intensity of ongoing tremors induced by physostigmine (111 mug I.C.), whereas, dopamine readily inhibited the latter. When superimposed, I.C. dopamine was equally effective in suppressing d-amphetamine tremor activity. The results emphasize the selective tremorogenic actions of d-amphetamine and call attention to the contrasting stabilizing role of dopamine. This would suggest that two types of adrenergic receptor sites are operative in the caudate in neuroregulation of involuntary movements.