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.
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ABSTRACT: There has been extensive work to elucidate the behavioral and physiological mechanisms responsible for taste preferences of the rat but little attempt to delineate the underlying genetic architecture. Here, we exploit the FHH-Chr n(BN)/Mcwi consomic rat strain set to identify chromosomes carrying genes responsible for taste preferences. We screened the parental Fawn Hooded Hypertensive (FHH) and Brown Norway (BN) strains and 22 FHH-Chr n(BN) consomic strains, with 96-h 2-bottle tests, involving a choice between water and each of the following 16 solutions: 10 mM NaCl, 237 mM NaCl, 32 mM CaCl(2), 1 mM saccharin, 100 mM NH(4)Cl, 32 mM sucrose, 100 mM KCl, 4% ethanol, 1 mM HCl, 10 mM monosodium glutamate, 1 mM citric acid, 32 microM quinine hydrochloride, 1% corn oil, 32 microM denatonium, 1% Polycose, and 1 microM capsaicin. Depending on the taste solution involved, between 1 and 16 chromosomes were implicated in the response. Few of these chromosomes carried genes believed to mediate taste transduction in the mouse, and many chromosomes with no candidate taste genes were revealed. The genetic architecture of taste preferences is considerably more complex than has heretofore been acknowledged.Chemical Senses 07/2010; 35(6):473-89. DOI:10.1093/chemse/bjq038 · 3.28 Impact Factor
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ABSTRACT: This study was undertaken to identify the neurochemical changes underlying the attenuation of voluntary ethanol intake induced by the cannabinoid CB1 receptor antagonist AM251 in fawn-hooded rats. Rats were exposed to the 2-bottle-choice paradigm (ethanol 10% v/v or water) for 15 days. After this period, rats received AM251 (3 to 6 mg/kg, i.p.) or vehicle. Voluntary ethanol intake decreased (30%) with the administration of incremental dosages of AM251 (3 mg/kg, 5 days and 6 mg/kg, 5 days) in rats with acquired high preferring ethanol consumption (>3.5 g of ethanol/kg/d). Ethanol intake significantly decreased proopiomelanocortin expression in the arcuate nucleus (38.31%) and micro-opioid-DAMGO-stimulated [(35)S]-GTPgamma binding in the caudate-putamen (40%), nucleus accumbens core (AccC) (32.87%), and shell (AccS) (34.21%). Moreover, ethanol intake increased tyrosine hydroxylase (TH) gene expression in the substantia nigra (24%) and ventral tegmental area (23%) and corticotrophin-releasing gene expression in the paraventricular hypothalamic nucleus (41.6%). The reduction of ethanol intake induced by AM251 was associated with blockade or significant reduction of the changes produced by ethanol in the expression of these genes in key regions related to drug dependence. Interestingly, treatment with AM251 reduced (20%) TH gene expression in rats drinking only water. In this respect, the action of AM251 in reducing TH gene expression may not be specific. Taken together, these results revealed that blockade of cannabinoid CB1 receptors (CB1r) decreased voluntary ethanol intake in ethanol-habituated rats by normalizing the neurochemical alterations induced by ethanol.Alcoholism Clinical and Experimental Research 10/2009; 34(1):131-41. DOI:10.1111/j.1530-0277.2009.01074.x · 3.31 Impact Factor
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ABSTRACT: This study examined the effect of fluoxetine, a selective serotonin (5-HT) reuptake inhibitor, on isolation-induced changes on sucrose consumption and preference, spontaneous open-field activity, forced swimming behavior, and on tissue levels of 5-HT and dopamine (DA) in hippocampus and ventral striatum (VS). Male Sprague-Dawley rats were reared in social isolation or group housing from postnatal day 28. Thirty-two days later, half of the isolated animals were orally treated with fluoxetine (10mg/kg/day) during the following 34 days. At the end of this period, behavior was assessed and afterward ex-vivo tissue samples were obtained. It was found that fluoxetine restored isolation-increased sucrose consumption and immobility behavior, without affecting locomotor activity, which appeared slightly increased in isolated groups both treated and untreated. In the hippocampus, isolation rearing depleted 5-HT contents and increased 3,4-dihydroxyphenylacetic acid (DOPAC) levels, as well as 5-HT and DA turnover. These neurochemical alterations were reversed by fluoxetine. In VS, treated and untreated isolated rats showed higher 5-HT levels than grouped congeners. Although fluoxetine did not affect 5-HT and DA contents in this region, it slightly reversed the alterations in the 5-HT and DA turnover observed in isolated rats. Overall, social isolation impaired incentive and escape motivated behaviors. At the neurochemical level, isolation rearing affected 5-HT rather than DA activity, and this differential effect was more noticeable in hippocampus than in VS. The chronic treatment with fluoxetine during the last month of rearing somewhat prevented these behavioral and neurochemical alterations. Our data suggest that isolation rearing is an appropriate procedure to model some developmental-related alterations underlying depression disorders.Behavioural brain research 12/2008; 198(1):199-205. DOI:10.1016/j.bbr.2008.10.036 · 3.39 Impact Factor