LSD but not lisuride disrupts prepulse inhibition in rats by activating the 5-HT2A receptorReportar como inadecuado

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, 208:179

First Online: 25 November 2009Received: 14 July 2009Accepted: 27 October 2009


RationaleCompounds that activate the 5-HT2A receptor, such as lysergic acid diethylamide LSD, act as hallucinogens in humans. One notable exception is the LSD congener lisuride, which does not have hallucinogenic effects in humans even though it is a potent 5-HT2A agonist. LSD and other hallucinogens have been shown to disrupt prepulse inhibition PPI, an operational measure of sensorimotor gating, by activating 5-HT2A receptors in rats.

ObjectiveWe tested whether lisuride disrupts PPI in male Sprague–Dawley rats. Experiments were also conducted to identify the mechanisms responsible for the effect of lisuride on PPI and to compare the effects of lisuride to those of LSD.

ResultsConfirming 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-HT2A 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-HT1A antagonist WAY-100635 but was prevented by pretreatment with the selective dopamine D2-D3 receptor antagonist raclopride 0.1 mg-kg, s.c.

ConclusionsThe effect of LSD on PPI is mediated by the 5-HT2A receptor, whereas activation of the 5-HT2A 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-HT2A agonist.

KeywordsHallucinogen Rats Prepulse inhibition 5-HT2A Lisuride LSD  Download fulltext PDF

Autor: Adam L. Halberstadt - Mark A. Geyer


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