Genetic animal models of depression and ethanol preference provide support for cholinergic and serotonergic involvement in depression and alcoholism.
The present article summarizes some comparative studies of the Fawn-Hooded (FH) rat, a potential animal model of ethanol preference, and the Flinders Sensitive Line (FSL) rat, a potential animal model of depression. Both FH and FSL rats exhibit high degrees of immobility in the forced swim test and have difficulty learning a two-way active avoidance task. However, there were no differences between the FH and FSL rats in the elevated plus maze. Studies of ethanol preference indicated high rates of ethanol intake (greater than 4 g/kg) and preference (greater than 50%) in the FH rats, but low rates of ethanol intake (less than 1.1 g/kg) and preference (less than 20%) in FSL rats. It is concluded that the FSL rats exhibit behaviors consistent with their being an animal model of depression, whereas the FH rats exhibit features consistent with their being an animal model of both depression and alcoholism. Psychopharmacological challenges indicated that both FSL and FH rats were more sensitive to the hypothermic effects of oxotremorine, a muscarinic agonist. However, FSL rats were also more sensitive to serotonergic agonists, and some of the present results and other investigators have reported serotonergic subsensitivity in the FH rats. Thus, FSL rats exhibit both cholinergic and serotonergic supersensitivity, whereas FH rats exhibit cholinergic supersensitivity but normal or reduced serotonergic sensitivity. Progeny from a genetic cross between FH and FSL rats exhibit cholinergic supersensitivity and have high ethanol preference scores. These data are consistent with genetic models suggesting that ethanol preference may be influenced by dominant genes, whereas cholinergic sensitivity may be influenced by recessive genes.
Overstreet
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Skipper Bowles Center for Alcohol Studies, University of North Carolina School of Medicine, Chapel Hill 27599-7175.
Rezvani
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Janowsky
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D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000428:Alcohol Drinking / Q000235:genetics* / Q000503:physiopathology; D000437:Alcoholism / Q000235:genetics* / Q000503:physiopathology; D000818:Animals; D001143:Arousal / Q000187:drug effects / Q000502:physiology; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D002065:Buspirone / Q000494:pharmacology; D003433:Crosses, Genetic; D003866:Depressive Disorder / Q000235:genetics* / Q000503:physiopathology; D004193:Discrimination Learning / Q000187:drug effects / Q000502:physiology; D004924:Escape Reaction / Q000187:drug effects / Q000502:physiology; D011939:Mental Recall / Q000187:drug effects / Q000502:physiology; D008957:Models, Genetic; D009949:Orientation / Q000187:drug effects / Q000502:physiology; D010095:Oxotremorine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011950:Receptors, Cholinergic / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D011985:Receptors, Serotonin / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D010879:Piperazines; D011950:Receptors, Cholinergic; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; D010095:Oxotremorine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C015068:1-(3-chlorophenyl)piperazine; D002065:Buspirone