Ritanserin-sensitive receptors modulate the prosocial and the anxiolytic effect of MDMA derivatives, DOB and PMA, in zebrafish

Little is known about the pharmacological effects of amphetamine derivatives. In the present study,
the effect on social preference and anxiety-like behavior of 2,5-dimetoxy-4-bromo-amphetamine
hydrobromide (DOB) and para-methoxyamphetamine (PMA), in comparison with 3,4 methylenedioxymethamphetamine
(MDMA) was investigated in zebrafish, an emerging model to study emotional
behavior in an inexpensive and quick manner. DOB (0.05-2 mg/kg), PMA (0.0005-2 mg/kg) or MDMA
(0.25-20 mg/kg), given i.m. to adult zebrafish, progressively increased the time spent in the proximity of
nacre fish picture in a social preference test. However, high doses were ineffective. Similarly, in the novel
tank diving and light-dark tests the compounds elicited a progressive anxiolytic effect in terms of time
spent in the upper half of the tank and in the light compartment, respectively. All the above effects were
interpolated by symmetrical parabolas. The 5-HT2A/C antagonist ritanserin (0.025-2.5 mg/kg) in association
with the maximal effective dose of MDMA, DOB and PMA blocked both the social and anxiolytic
effect. Taken together these findings demonstrate for the first time the prosocial and anxiolytic properties
of DOB and PMA and focus on the mechanisms of their action through the serotonergic-like system
suggesting a potential clinical application.