Evidence for the functional interaction of two central neurotransmitters

Rats pretreated with pargyline (50 mg/kg) and then given either l-tryptophan (150 mg/kg) or l-Dopa (100 mg/kg) display strikingly similar behavioral syndromes. Especially prominent are tremor, rigidity, lateral head weaving and reciprocal forepaw treading. Because of the overt similarity in these 2 syndromes, it was hypothesized that they might be dependent upon a common neurochemical substrate. This was tested by observing whether blocking either the biosynthesis of serotonin or dopamine or their receptors was capable of blocking the production of the syndrome produced by precursors of the other transmitter. Pretreatment with α-methyl-p-tyrosine, a catecholamine synthesis inhibitor, failed to affect either syndrome, whereas p-chlorophenylalanine, a serotonin synthesis inhibitor, blocked both. Similarly, the dopamine receptor blocker pimozide had no effect on either syndrome, while the serotonin receptor blockers cinanserin and methysergide blocked or markedly diminished both syndromes equally. It is concluded that at least a portion of the syndrome that emerges following pargyline and l-Dopa is mediated by serotonin rather than dopamine.