MK-801- and ethanol-induced activity in inbred long-sleep and short-sleep mice: dopamine and serotonin systems

• Published in: European journal of pharmacology 2002-12, Vol.457 (2), p.125-135
• Main Authors: Hanania, Taleen, McCreary, Andrew C, Haughey, Heather M, Salaz, Danielle O, Zahniser, Nancy R
• Format: Article
• Language: English
• Subjects: 5-HT (serotonin) 5-Hydroxytryptamine; Animals; Benzazepines - pharmacology; Binding Sites; Biological and medical sciences; Cerebral Cortex - metabolism; Cerebral Cortex - physiology; Citalopram - pharmacology; Dizocilpine Maleate - pharmacology; Dopamine; Dopamine Antagonists - pharmacology; Ethanol; Ethanol - pharmacology; Genotype; Hippocampus - metabolism; Hippocampus - physiology; Locomotor activity; Male; Medical sciences; Mice; Mice, Inbred Strains; MK-801; Motor Activity - drug effects; Motor Activity - physiology; Neuropharmacology; NMDA receptor; Pharmacology. Drug treatments; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Receptors, Dopamine - metabolism; Receptors, Dopamine - physiology; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors; Receptors, Serotonin - metabolism; Receptors, Serotonin - physiology; Serotonin Uptake Inhibitors - pharmacology; Sleep - genetics; Sleep - physiology; Time Factors
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(02)02685-7

Low doses of (5 R,10 S)-(+)-5-methyl-10,11-dihydro-5 H-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.