Relevant properties have been detected in protein fraction (LP) isolated from latex of Calotropis procera. In order to best characterize LP potentiality, this work describes some effects of LP on central nervous system (CNS). Three models were performed: elevated plus maze (EPM), open field (OF), and hole-board (HB) tests. LP was administered intraperitoneally to male mice. To assess the probable action mechanism, drugs acting on glutamatergic (ketamine, i.p.), gabaergic (diazepam and flumazenil, i.p.) and dopaminergic (haloperidol, i.p.) systems were used on OF. Decreases in the number of entries in the open and closed arms of EPM were observed at 100 mg/kg and this effect may be due to the reduction in the locomotor activity previously observed. A reduction in locomotor activity was observed in animals which received LP 50 and 100 mg/kg. There was a decrease in rearing at all doses; a reduction in grooming was seen only at 50 and 100 mg/kg. Ketamine reversed the effects of LP, and haloperidol reinforced the hypolocomotor effects of LP. In HB, there was a decrease in the number of head dips after LP 100 mg/kg; such effect may also be due to the reduction of the locomotor activity. The results suggest that LP from C. procera have depressant effects on the CNS, but do not present any anxiolytic effect. These effects may reflect a dopaminergic action. The active doses were considerably higher than those observed for anticancer, anti-inflammatory and anti-nociceptive activities described in the literature.