title: Diurnal variation in nicotine sensitivity in mice: role of genetic background and melatonin.
abstract: Despite the evidence that there is a daily rhythm in smoking behavior and that the effects of drugs of abuse exhibit diurnal variations, very few studies have explored the extent to which sensitivity to the effects of nicotine vary over the course of the day. In the studies described in this report, the melatonin proficient mouse strain C3H/Ibg and the melatonin deficient mouse strains C57BL/6J and DBA/2J were assessed for diurnal variations in sensitivity to the effects of nicotine. Results indicated that there is significant variation in sensitivity to both activity and body temperature depressant effects of nicotine in the melatonin proficient C3H/Ibg strain with maximal sensitivity occurring during the latter third of the light period of the light cycle and minimal sensitivity taking place during the last third of the dark phase of the light cycle. The melatonin deficient strains did not exhibit diurnal differences in sensitivity to the effects of nicotine suggesting a potential role for melatonin in modulating the effects of nicotine. Experiments with knockout mice lacking both the Mtnr1a and Mtnr1b melatonin receptors confirmed that the reduced sensitivity observed during the dark phase is melatonin dependent. Diurnal variation in nicotinic receptor expression also was measured in cortex, hippocampus, hypothalamus and striatum using [(125)I]-α-bungarotoxin and [(125)I]-epibatidine. [(125)I]-α-bungarotoxin binding in hypothalamus of C3H mice exhibited a diurnal pattern with maximal binding observed in the latter third of the light portion of the light cycle. No other significant differences in binding were detected.
authors: Institute for Behavioral Genetics, University of Colorado, Boulder, CO 80309, USA.
authors: Sharon
authors: S
authors: Mexal
authors: William J
authors: WJ
authors: Horton
authors: Eric L
authors: EL
authors: Crouch
authors: Sheila I B
authors: SI
authors: Maier
authors: Andra L
authors: AL
authors: Wilkinson
authors: Marisa
authors: M
authors: Marsolek
authors: Jerry A
authors: JA
authors: Stitzel
mesh_terms: D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000378:metabolism; D002038:Bungarotoxins / Q000378:metabolism; D002940:Circadian Rhythm / Q000235:genetics* / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008550:Melatonin / Q000502:physiology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D011725:Pyridines / Q000378:metabolism; D011869:Radioligand Assay; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism; D012727:Sex Characteristics; D015398:Signal Transduction / Q000502:physiology; D013045:Species Specificity
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D002038:Bungarotoxins; D018722:Nicotinic Agonists; D011725:Pyridines; D011978:Receptors, Nicotinic; D009538:Nicotine; D008550:Melatonin; C082748:epibatidine