Potentiation of DOI-induced forward locomotion in rats by (-)-pindolol pretreatment

The present experiments were undertaken in order to examine mechanisms of action for reported interactions between the beta-blocker (-)-pindolol and serotonergic agents. It was found that pretreatment with (-)-pindolol (2 mg kg-1 s.c.) potentiated the stereotyped forward locomotion induced by the 5-HT2A/C receptor agonist DOI (0.125-1.0 mg kg-1 s.c.) in rats observed in an open-field arena. This (-)-pindolol/DOI-induced stereotyped forward locomotion was fully antagonized by the 5-HT2A/C receptor antagonist ritanserin (2 mg kg-1 s.c.), suggesting that (-)-pindolol enhances serotonin release, resulting i.a. in postsynaptic 5-HT2A/C receptor activation. This effect by (-)-pindolol is in all probability indirect since this compound lacks affinity for 5-HT2A/C receptors, and could be explained by reported antagonism of inhibitory serotonergic somato-dendritic 5-HT1A autoreceptors, although other possibilities related to 5-HT1B receptors or beta-adrenoceptors can not be excluded at this time. Furthermore, (-)-pindolol treatment also enhanced 5-HTP-induced (12.5-100 mg kg-1 i.p.) effects on spontaneous motor activity. These effects, however, were of smaller magnitude, and less consistent than those seen in combination with DOI.