Effects of cocaine treatment on the nervous system of planaria (Dugesia gonocephala s. l.). Histochemical and ultrastructural observations.

Acute high dose treatment with cocaine in planaria has been shown to produce hyperkinesia followed by immobilization, thus suggesting progressive neuronal dopamine (DA) depletion. On the contrary, treatment with low doses of cocaine inhibits motor activity in planaria, without producing hyperkinesias. Here we investigated the morpho-functional changes of the DA presynaptic terminals following cocaine treatment in planaria (acute high dose and chronic low dose). Neuronal DA content was determined by means of histochemical methods, and nerve cell ultrastructure was examined by electron microscopy. The effects of cocaine were compared to those of L-dopa, reserpine (used as positive and negative controls, respectively) and normal untreated specimens. Presynaptic vesicles and DA content were significantly reduced by chronic low-dose cocaine treatment. These effects were even more robust when the drug was acutely administered at high dose. Thus, depletion of DA vesicles is produced by cocaine in planaria, as well as in mammals. The behavioral effects of chronic low-dose treatment with cocaine, however, suggest that the drug acts not only as a DA reuptake blocker, but also as a direct agonist on presynaptic DA receptors. Acute high-dose administration of cocaine also produced signs of neuronal suffering, thus providing evidence for a direct neurotoxic effect of the drug.