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 receptors, WAY 100135, was capable of modifying the psychostimulant and psychotomimetic effects of MK-801, a non-competitive antagonist of NMDA receptors. It 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 effect on the locomotor activity of rats; 2) WAY 100135 (1.25 and 2.5 mg/kg, but not 10 or 20 mg/kg), attenuated or abolished the disruptive effects of MK-801 on the sensorimotor gating measured in a prepulse-induced inhibition of the acoustic startle response paradigm. WAY 100135 in all tested doses had no effect on the sensorimotor gating or amplitude of the acoustic startle 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, measured in a delayed alternation task. Again, given alone, WAY 100135 did not 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 hippocampus, measured 2 and 24 hours after MK-801 administration. These data indicate that 5-HT1A receptors might be involved in the psychotomimetic effects of non-competitive NMDA receptor antagonists. In addition, 5-HT1A serotonin receptor antagonists and partial agonists may have potential antipsychotic properties.
Wedzony
K
K
Institute of Pharmacology, Polish Academy of Sciences,., Kraków, Poland.
Maćkowiak
M
M
Zajaczkowski
W
W
Fijał
K
K
Chocyk
A
A
Czyrak
A
A
D000818:Animals; D016291:Dizocilpine Maleate / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D006213:Hallucinogens / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D006651:Histocytochemistry; D017403:In Situ Hybridization; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology*; D011597:Psychomotor Performance / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects*; D044263:Receptors, Serotonin, 5-HT1; D013216:Reflex, Startle / Q000187:drug effects; D012702:Serotonin Antagonists / Q000494:pharmacology*
D006213:Hallucinogens; D018696:Neuroprotective Agents; D010879:Piperazines; D012333:RNA, Messenger; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; C081293:WAY 100135; D016291:Dizocilpine Maleate