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.
Brain Behavior and Immunity 08/2011; 25. DOI:10.1016/j.bbi.2011.07.131 · 6.13 Impact Factor
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ABSTRACT: Viral infection of the CNS can result in encephalitis and acute seizures, increasing the risk for later-life epilepsy. We have previously characterized a novel animal model of temporal lobe epilepsy that recapitulates key sequela in the development of epilepsy following viral infection. C57BL/6J mice inoculated with the Daniel's strain of Theiler's Murine Encephalomyelitis Virus (TMEV; 3×10(5) PFU, i.c.) display acute limbic seizures that secondarily generalize. A majority of acutely seized animals develop spontaneous seizures weeks to months later. As part of our investigation, we sought to assess behavioral comorbidity following TMEV inoculation. Anxiety, depression, cognitive impairment, and certain psychoses are diagnosed in persons with epilepsy at rates far more frequent than in the general population. We used a battery of behavioral tests to assess anxiety, depression, cognitive impairment, and general health in acutely seized animals inoculated with TMEV and compared behavioral outcomes against age-matched controls receiving a sham injection. We determined TMEV-seized animals are less likely to move through the exposed center of an open field and are less likely to enter into the lighted half of a light/dark box; both behaviors may be indicative of anxiety-like behavior. TMEV-seized animals also display early and persistent reductions in novel object exploration during novel object place tasks and do not improve in their ability to find a hidden escape platform in Morris water maze testing, indicative of impairment in episodic and spatial memory, respectively. Cresyl violet staining at 35 and 250 days after injection reveals bilateral reductions in hippocampal area, with extensive sclerosis of CA1 evident bilaterally along the rostral-caudal axis. Early and persistent behavioral changes in the TMEV model provide surrogate markers for assessing disease progression as well as endpoints in screening for the efficacy of novel compounds to manage both seizure burden and comorbid conditions.Neurobiology of Disease 01/2014; DOI:10.1016/j.nbd.2013.12.015 · 5.62 Impact Factor
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ABSTRACT: Aim:Brucine (BRU) extracted from the seeds of Strychnos nux-vomica L is glycine receptor antagonist. We hypothesize that BRU may modify alcohol consumption by acting at glycine receptors, and evaluated the pharmacodynamic profiles and adverse effects of BRU in rat models of alcohol abuse.Methods:Alcohol-preferring Fawn-Hooded (FH/Wjd) rats were administered BRU (10, 20 or 30 mg/kg, sc). The effects of BRU on alcohol consumption were examined in ethanol 2-bottle-choice drinking paradigm, ethanol/sucrose operant self-administration paradigm and 5-d ethanol deprivation test. In addition, open field test was used to assess the general locomotor activity of FH/Wjd rats, and conditioned place preference (CPP) was conducted to assess conditioned reinforcing effect.Results:In ethanol 2-bottle-choice drinking paradigm, treatment with BRU for 10 consecutive days dose-dependently decreased the ethanol intake associated with a compensatory increase of water intake, but unchanged the daily total fluid intake and body weight. In ethanol/sucrose operant self-administration paradigms, BRU (30 mg/kg) administered before each testing session significantly decreased the number of lever presses for ethanol and the ethanol intake, without affecting the number of sucrose (10%) responses, total sucrose intake, and the number of lever presses for water. Acute treatment with BRU (30 mg/kg) completely suppressed the deprivation-induced elevation of ethanol consumption. Treatment with BRU (10, 20, and 30 mg/kg) did not alter locomotion of FH/Wjd rats, nor did it produce place preference or aversion.Conclusion:BRU selectively decreases ethanol consumption with minimal adverse effects. Therefore, BRU may represent a new pharmacotherapy for alcoholism.Acta Pharmacologica Sinica 06/2014; 35(7). DOI:10.1038/aps.2014.28 · 2.50 Impact Factor