5-HT(3) receptors, alcohol and aggressive behavior in mice.
Alcohol is a positive modulator at the 5-HT(3) receptor, which has been implicated in alcohol drinking, anxiety and aggression. The reported experiments explored the role of the 5-HT(3) receptor in aggressive behavior and alcohol-heightened aggression. Male, CFW mice were trained to self-administer 1.0 g/kg of alcohol, after which they confronted an intruder. Half of the CFW mice exhibited consistently increased aggressive behavior after alcohol and were designated as showing alcohol-heightened aggression, the others showed no increase and were designated as showing alcohol non-heightened aggression. The 5-HT(3) antagonist, ondansetron (0.01-1.0 mg/kg), significantly reduced aggression in both groups of CFW mice without affecting non-aggressive behaviors. Zacopride also reduced aggression effectively in both groups of mice, but at high doses began to affect walking. Male B6SJL/F2 transgenic 5-HT(3) over-expressing mice (TG) and wild-type mice (WT) were tested for aggressive behavior in their home cage. In those individuals that fought in tests of resident-intruder aggression, no differences were found in aggression after alcohol intake. In tests of aggression without alcohol intake, zacopride reduced aggression in both TG and WT mice at a dose of 56 mg/kg. Antagonism of 5-HT(3) receptors shows promising anti-aggressive effects, although these effects depend on the genetic background of the mice.
McKenzie-Quirk
S D
SD
Department of Psychology, Tufts University, Medford, Massachusetts 02155, USA.
Girasa
K A
KA
Allan
A M
AM
Miczek
K A
KA
D000374:Aggression / Q000187:drug effects*; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D051379:Mice; D017294:Ondansetron / Q000494:pharmacology; D044406:Receptors, Serotonin, 5-HT3 / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology
D001549:Benzamides; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002492:Central Nervous System Depressants; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists; D000431:Ethanol; D017294:Ondansetron; C055971:zacopride