Interactions of 5HT reuptake inhibitors and ethanol in tests of exploration and anxiety.
Treatment with 5HT reuptake inhibitors has been shown to attenuate ethanol consumption in both animals and humans. These experiments investigate in mice the interactions of the 5HT reuptake inhibitors fluoxetine, citalopram and fluvoxamine and the NA uptake inhibitor desipramine with ethanol in the holeboard test and the elevated plusmaze test of anxiety. Ethanol (2.4 g/kg) increased activity both in the holeboard and on the plusmaze, decreased both the number and duration of head-dips in the holeboard, and increased both the percentage time and percentage entries on to the open-arm of the plusmaze (reflecting its anxiolytic properties). On their own, the selective 5HT uptake inhibitors fluoxetine, fluvoxamine, and citalopram and the NA uptake inhibitor desipramine (10-20 mg/kg) did not significantly alter any of the behavioral measures. The only consistent interaction was seen with fluoxetine which reduced ethanol's anxiolytic effects at the 20 mg/kg dose without altering ethanol's effects on exploration or locomotion. The results suggest that the attenuation of ethanol's anxiolytic properties by fluoxetine may not be serotonin related since other 5HT reuptake inhibitors did not show this effect at the doses used.
Durcan
M J
MJ
Division of Intramural Clinical and Biological Research, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892.
Lister
R G
RG
Eckardt
M J
MJ
Linnoila
M
M
D000818:Animals; D001007:Anxiety / Q000503:physiopathology; D015283:Citalopram / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology*; D005106:Exploratory Behavior / Q000187:drug effects; D005473:Fluoxetine / Q000494:pharmacology; D016666:Fluvoxamine; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects; D010091:Oximes / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology*
D010091:Oximes; D012702:Serotonin Antagonists; D005473:Fluoxetine; D015283:Citalopram; D000431:Ethanol; D016666:Fluvoxamine; D003891:Desipramine