MK-801- and ethanol-induced activity in inbred long-sleep and short-sleep mice: dopamine and serotonin systems.
Low doses of (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801; dizocilpine) or ethanol induce less locomotor activation in inbred long-sleep (ILS) than short-sleep (ISS) mice. These differences may involve altered dopamine and/or 5-hydroxytryptamine (serotonin; 5-HT) neurotransmission. To address this possibility, the dopaminergic and serotonergic mechanisms underlying the locomotor-stimulant effects of MK-801 and ethanol in ILS and ISS mice were studied. Dopamine D1, D2 and 5-HT(2A) receptor antagonists reduced MK-801-stimulated activity in ILS mice without having any effect in ISS mice. The 5-HT reuptake inhibitor fluoxetine potentiated MK-801-stimulated activity selectively in ILS mice. Strain differences in 5-HT transporters do not explain this selective effect of fluoxetine in ILS mice since [3H]citalopram binding and [3H]5-HT uptake studies found no differences in the affinity, number or function of 5-HT transporters between ILS and ISS mice. Ethanol-induced activity in ISS mice was depressed by dopamine D2 and 5-HT(2C) receptor antagonists and enhanced by a 5-HT(1A) receptor antagonist. These results suggest that in ILS mice the locomotor-stimulant effects of MK-801 require increased dopamine and/or 5-HT neurotransmission. Conversely, in ISS mice, the effects of MK-801 appear to be monoamine-independent. Thus, even though both MK-801 and ethanol inhibit N-methyl-D-aspartate receptors, their stimulant effects appear to involve different neuronal systems.
Hanania
Taleen
T
Department of Pharmacology C-236, University of Colorado Health Sciences Center, 4200 E. Ninth Avenue, Denver, CO 80262, USA. Taleen.Hanania@UCHSC.edu
McCreary
Andrew C
AC
Haughey
Heather M
HM
Salaz
Danielle O
DO
Zahniser
Nancy R
NR
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D001665:Binding Sites; D002540:Cerebral Cortex / Q000378:metabolism / Q000502:physiology; D015283:Citalopram / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D005838:Genotype; D006624:Hippocampus / Q000378:metabolism / Q000502:physiology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D011954:Receptors, Dopamine / Q000378:metabolism / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D011985:Receptors, Serotonin / Q000378:metabolism / Q000502:physiology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D012890:Sleep / Q000235:genetics / Q000502:physiology*; D013997:Time Factors
D001552:Benzazepines; D015283:Citalopram; D016291:Dizocilpine Maleate; D018492:Dopamine Antagonists; D000431:Ethanol; D011954:Receptors, Dopamine; D016194:Receptors, N-Methyl-D-Aspartate; D011985:Receptors, Serotonin; D017367:Selective Serotonin Reuptake Inhibitors