Characterization of the disruptions of prepulse inhibition and habituation of startle induced by alpha-ethyltryptamine.
Alpha-ethyltryptamine (AET), a monoamine oxidase inhibitor and potent monoamine releasing agent, has been sold illicitly as a substitute for the entactogen 3,4-methylenedioxy-N-methylamphetamine (MDMA), and is the first example of an indolealkylamine analog demonstrated to substitute in MDMA-trained animals. Previous studies have demonstrated that MDMA and AET have similar effects on unconditioned motor behavior in rats. Furthermore, the locomotor-activating effects of both MDMA and AET are blocked by pretreatment with fluoxetine, a selective serotonin (5-HT) uptake inhibitor, suggesting that the two compounds may share a presynaptic mechanism of action. This study examined the effects of AET using measures of startle plasticity, specifically prepulse inhibition (PPI), and habituation. PPI, a measure of sensorimotor gating, is reduced in rats treated with hallucinogens, 5-HT releasers, and dopamine agonists. In contrast, startle habituation is reduced in rats treated with hallucinogens and 5-HT releasers. AET (1.25, 2.5, 5, and 10 mg/kg) decreased PPI of acoustic startle and reduced the habituation of tactile startle. To determine whether AET produces these effects via pre- or postsynaptic actions, fluoxetine (10 mg/kg) was used as a pretreatment. By itself, fluoxetine did not disrupt PPI, but did reduce startle habituation. Fluoxetine pretreatment prevented the AET-induced disruption of PPI and reduced the AET-induced disruption of startle habituation. Combined with previous findings, these results confirm that AET produces behavioral effects that mimic those of other indirect 5-HT agonists and that the effects of AET on startle plasticity are due to the release of presynaptic 5-HT.
Martinez
D L
DL
Department of Neuroscience, University of California, San Diego, La Jolla 92093-0804, USA.
Geyer
M A
MA
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005473:Fluoxetine / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000187:drug effects*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D014363:Tryptamines / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D017366:Serotonin Receptor Agonists; D014363:Tryptamines; D005473:Fluoxetine; C038034:etryptamine