Behavioral effects of psychollatine, a new glycoside indole monoterpene alkaloid isolated from Psychotria umbellata, was investigated in models of anxiety, depression, memory, tremor, and sedation related to 5-HT and/or GABA neurotransmission. The GABA antagonist picrotoxin and the 5-HT2 antagonist ritanserin were used to examine the role of GABA and 5-HT2 receptors in psychollatine-induced effects. In the light/dark and hole-board models of anxiety, diazepam (0.75 mg/kg) and psychollatine (7.5 and 15 mg/kg) showed anxiolytic-like effect at doses that do not increase sleeping time nor alter spontaneous locomotor activity. The anxiolytic effect of psychollatine was prevented by prior administration of ritanserin, but not of picrotoxin, indicating that 5-HT2 but not GABA receptors are implicated. In the forced swimming model of depression, psychollatine (3 and 7.5 mg/kg) effects were comparable to the antidepressants imipramine (15 mg/kg) and fluoxetine (20 mg/kg). Psychollatine suppressed oxotremorine-induced tremors in all doses. In the step-down learning paradigm, diazepam (0.85 mg/kg), MK-801 (0.15 mg/kg), and psychollatine 100 mg/kg impaired the acquisition of learning and memory consolidation, without interfering with retrieval. It is concluded that the effects of psychollatine at the central nervous system involve serotonergic 5HT2(A/C) receptors.

Psychollatine (1), a new glycoside indole monoterpene alkaloid isolated from Psychotria umbellata, has shown an interesting psychopharmacological profile. This study aimed to investigate the role of NMDA glutamate and dopamine receptors in mediating the properties of 1. Psychollatine (1) was assessed for NMDA-induced seizures, MK-801-induced hyperlocomotion, amphetamine-induced lethality, and apomorphine-induced climbing behavior in mice. Psychollatine (1) (100 mg/kg) and MK-801 (0.3 mg/kg) prevented NMDA-induced seizures (P < 0.01), while 1 (100 mg/kg) attenuated the MK-801-induced hyperlocomotion (P < 0.05). Compound 1 (3 and 10 mg/kg), as well as chlorpromazine (4 mg/kg), prevented amphetamine-induced lethality (P < 0.05). Finally, 1 (10 mg/kg) (P < 0.05), MK-801 (0.2 mg/kg) (P < 0.01), and chlorpromazine (4 mg/kg) (P < 0.01) attenuated apomorphine-induced climbing behavior. The present results strongly support the involvement of NMDA glutamate receptors in the mode of action of psychollatine (1).