WAY 100135, an antagonist of 5-HT1A serotonin receptors, attenuates psychotomimetic effects of MK-801

In the present study, we investigated whether the antagonist of 5-HT1A rece ptors, WAY 100135, was capable of modifying the psychostimulant and psychot omimetic effects of MK-801, a non-competitive antagonist of NMDA receptors. If was found that: 1) WAY 100135 (10 and 20 mg/kg, but not 1.25, 2.5, and 5 mg/kg) transiently, in a dose dependent manner, attenuated the locomotor stimulant effects of MK-801 (0.4 mg/kg). Given alone, WAY 100135 had no eff ect on the locomotor activity of rats; 2) WAY 100135 (1.25 and 2.5 mg/kg, b ut not 10 or 20 mg/kg), attenuated or abolished the disruptive effects of M K-801 on the sensorimotor gating measured in a prepulse-induced inhibition of the acoustic startle response paradigm. WAY 100135 in all tested doses h ad no effect on the sensorimotor gating or amplitude of the acoustic startl e response; 3) WAY 100135 (1.25, 2.5 mg/kg, but not 5 mg/kg) attenuated the detrimental effects of MK-801 on working memory and selective attention, m easured in a delayed alternation task. Again, given alone, WAY 100135 did n ot influence the behavior of rats in that experimental paradigm; and 4) MK- 801 (0.4 mg/kg) had no effect on the 5-HT1A receptor mRNA level in rat hipp ocampus, measured 2 and 24 hours after MK-801 administration. These data in dicate that 5-HT1A recptors might be involved in the psychotomimetic effect s of non-competitive NMDA receptor antagonists. In addition, 5-HT1A seroton in receptor antagonists and partial agonists may have potential antipsychot ic properties. (C) 2000 American College of Neuropsychopharmacology. Publis hed by Elsevier Science Inc. All rights reserved.