The Fawn-Hooded (FH/Wjd) rat: a genetic animal model of comorbid depression and alcoholism.

The Fawn-Hooded (FH/Wjd) rat is an inbred strain of rat that has been reported to exhibit both high immobility in the forced swim test and high voluntary ethanol intake, measures that have been periodically linked with depression and alcoholism in humans. The present paper will first present a survey of the literature and previously unpublished findings that bear on the question of whether FH/Wjd rats should be considered genetic animal models of depression and alcoholism. Subsequently, behavioral studies of the FH/Wjd rats, the non-drinking ACI/N strain, and their F1 and F2 intercrosses will be described. Under free choice conditions, the FH/Wjd rat drinks up to 6 g/kg 10% ethanol per day. This intake was sufficient to render the rats tolerant to the hypothermic effects of injected ethanol (2.5 g/kg). Rats that had been voluntarily drinking for at least 6 weeks also exhibited withdrawal-induced anxiety in the social interaction, elevated plus maze, and ultrasonic vocalization tasks. The FH/Wjd rat exhibits a 25-30% increase in alcohol intake when the alcohol is returned after a 24-h period of deprivation. It responds to drugs that are effective in humans with a reduction in alcohol intake. Therefore, the FH/Wjd rat meets most of the criteria for an animal model of alcoholism. Chronic antidepressant treatments correct several of the abnormalities exhibited by the FH/Wjd rats, including the exaggerated immobility in the forced swim test. Therefore, the FH/Wjd rats also fulfill some of the criteria for an animal model of depression. On the contrary, inbred ACI/N rats do not drink much alcohol voluntarily and are quite active in the forced swim test. The FH/Wjd and ACI/N rats were intercrossed to obtain the F1 and F2 progenies, which were then tested for alcohol intake and immobility. Alcohol intake and immobility were distributed in different patterns in the F1 and F2 progenies. Alcohol intake was intermediate in the F1 progeny, while immobility was closer to the FH/Wjd parents. In the F2 progeny, chi-square analyses indicated that the distributions were significantly different. In addition, there were no significant litter effects, indicating that maternal effects did not appear to occur. There were also no significant differences among rats with different coat colors, suggesting that the Fawn-Hooded phenotype can be separated from the measures of alcohol intake and immobility. We conclude that the FH/Wjd rat is a genetic animal model of depression and alcoholism, but that the two measures reflective of these states are under separate genetic controls.