Depressive-like behavior and high alcohol drinking co-occur in the FH/WJD rat but appear to be under independent genetic control

Abstract

This review will consider the evidence supporting the view that a specific substrain of Fawn-Hooded rat (FH/Wjd) exhibits co-occurring depressive-like behavior and high alcohol intake independently. First, the FH/Wjd rat is compared with other Fawn-Hooded substrains (FH/Har, FHH/Eur, FHL/Eur) and it is concluded that only the FH/Wjd rat is both highly immobile in the forced swim test and drinks substantial amounts of 5–10% alcohol voluntarily. Next it is demonstrated that the FH/Wjd rat fulfils many of the criteria proposed for an animal model of alcoholism (becomes tolerant, becomes dependent and expresses withdrawal symptoms, bar-presses for alcohol). Other literature in addition to the high swim test immobility suggests that the FH/Wjd rat may also be an animal model of depression (high basal corticosterone levels, blunted hormonal responses to serotonergic agonists). To study the phenotypes more closely an inbred strain (ACI/N) of rat that drank little alcohol voluntarily and exhibited considerable swimming in the forced swim test (i.e., low immobility) was obtained. A systematic intercrossing of the parental strains and the resulting F1 progeny was carried out to generate more than 800 F2s. Swim test immobility, alcohol intake and preference and saccharin intake are four of the 7 variables assessed in each of these rats. Using classical quantitative genetics methods, it was determined that these four phenotypes exhibited modest heritability and were influenced by multiple genes. Correlation coefficients between immobility and the other measures were near zero, whereas alcohol intake and preference were highly correlated ( r = 0.9 ) and alcohol and saccharin intakes were modestly correlated ( r = 0.3 ). A final study showed that chronic fluoxetine treatment counteracted the high immobility but did not affect alcohol intake, similar to human studies. These findings suggest that although depressive-like behavior and high alcohol intake co-occur in the FH/Wjd rat, they are independently regulated.