Conclusions
The effect of LSD on PPI is mediated by the 5-HT(2A) receptor, whereas activation of the 5-HT(2A) receptor does not appear to contribute to the effect of lisuride on PPI. These findings demonstrate that lisuride and LSD disrupt PPI via distinct receptor mechanisms and provide additional support for the classification of lisuride as a non-hallucinogenic 5-HT(2A) agonist.
Objective
We tested whether lisuride disrupts PPI in male Sprague-Dawley rats. Experiments were also conducted to identify the mechanism(s) responsible for the effect of lisuride on PPI and to compare the effects of lisuride to those of LSD.
Results
Confirming a previous report, LSD (0.05, 0.1, and 0.2 mg/kg, s.c.) reduced PPI, and the effect of LSD was blocked by pretreatment with the selective 5-HT(2A) antagonist MDL 11,939. Administration of lisuride (0.0375, 0.075, and 0.15 mg/kg, s.c.) also reduced PPI. However, the PPI disruption induced by lisuride (0.075 mg/kg) was not blocked by pretreatment with MDL 11,939 or the selective 5-HT(1A) antagonist WAY-100635 but was prevented by pretreatment with the selective dopamine D(2)/D(3) receptor antagonist raclopride (0.1 mg/kg, s.c). Conclusions: The effect of LSD on PPI is mediated by the 5-HT(2A) receptor, whereas activation of the 5-HT(2A) receptor does not appear to contribute to the effect of lisuride on PPI. These findings demonstrate that lisuride and LSD disrupt PPI via distinct receptor mechanisms and provide additional support for the classification of lisuride as a non-hallucinogenic 5-HT(2A) agonist.