Comparison of alcohol-preferring and nonpreferring selectively bred rat lines. I. Ethanol initiation and limited access operant self-administration

Several lines of alcohol-preferring and alcohol-nonpreferring rats have been developed using selective breeding based on 24-hr homecage ethanol consumption. However, it remains unclear if the selection based on two-bottle choice resulted in similar ethanol self-administration when measured using an operant procedure. In this paper, we compare our previous work using alcohol-accepting (AA) and alcohol-nonaccepting (ANA) rats with data obtained using the identical procedures in the (P) and (NP) rat lines, and both replicate lines of the high alcohol drinking (HAD1 and HAD2) and low alcohol drinking (LAD1 and LAD2) lines. All rats from each line were initiated to self-administer 10% ethanol using the sucrose fading procedure. After initiation, increasing concentrations of ethanol up to 30% ethanol were tested. The results indicated that only in the LAD1 and LAD2 lines was ethanol presentation not able to maintain lever pressing after initiation. Compared with the AA line, the P, HAD1, HAD2, and NP lines all self-administered more ethanol in the operant paradigm after initiation. The ANA line self-administered less ethanol than the AA line, but more than the LAD lines. Correlational analysis of homecage consumption with operant ethanol self-administration suggested that approximately 62% of the genetic variance in operant self-administration resulted from genes selected for the homecage drinking. At the same time, it was clear that there were genetic influences on operant self-administration that were not selected for by homecage ethanol drinking.     

Differential rearing conditions and alcohol-preferring rats: Consumption of and operant responding for ethanol.

Exposing rats to differential rearing conditions during early postweaning development has been shown to produce changes in a number of behaviors displayed during adulthood. The purpose of the present studies was to investigate whether rearing alcohol-preferring (P) and nonpreferring (NP) rats in an environmental enrichment condition (EC), a social condition (SC), or an impoverished condition (IC) would differentially affect self-administration of 10% ethanol. In Experiment 1, rats were tested for consumption of 10% ethanol in limited- and free-access tests. For Experiment 2, rats were trained to respond in an operant chamber for ethanol and then provided concurrent access to 10% ethanol and water. Each solution was presented in a separate liquid dipper after meeting the schedule of reinforcement on distinct levers. After concurrent access tests, the water lever/dipper was inactivated and a progressive ratio (PR) schedule was initiated. Three successive solutions (10% ethanol, 15% ethanol, and 10% sucrose) were tested under the PR. For P rats, rearing in an EC reduced ethanol consumption, preference, and motivation to obtain ethanol, relative to P rats reared in an IC. Thus, exposure to a novel environment immediately after weaning acted to decrease the reinforcing properties of ethanol in an animal model for alcoholism. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Acamprosate and alcohol: I. Effects on alcohol intake following alcohol deprivation in the rat

Acamprosate (calcium-acetyl homotaurinate) is a new compound in the treatment of alcoholism. Its efficacy has been proven in several clinical trials and registration is now pending in most European countries. The basic mechanisms by which acamprosate elicits its anti-craving action, thereby leading to reduced relapse rates, is not known at the moment. In the present study we describe a rat model of long-term alcohol-drinking which mimics relapse behavior in human alcoholics. The effect of acamprosate was studied in this model. Wistar rats had a free choice between water and alcohol solutions of different concentrations (5, 10, 20% v/v). After two months of continuous alcohol access, rats were deprived of alcohol for three days. Following this deprivation phase, all alcohol solutions were presented again. This procedure was repeated monthly for the following six months. The rats consumed 3.5 +/- 0.3 g/kg alcohol a day. After alcohol deprivation, alcohol intake rose to 5.2 +/- 0.3 g/kg per day resulting in blood alcohol levels of 30 +/- 6 mg/dl. Interestingly, the addition of quinine to the alcohol solutions or the additional presentation of a 5% sucrose solution did not affect the alcohol-deprivation effect after eight months of this intermittent alcohol exposure. However, when acamprosate (50-200 mg/kg i.p.) was administered twice daily, alcohol-drinking following an alcohol-deprivation phase was decreased dose dependently. Given at the highest dose alcohol intake even dropped significantly below baseline drinking. Together, these results show that acamprosate effectively diminishes the alcohol-deprivation effect. Furthermore, the described model seems to be a suitable animal model to screen compounds for their anti-relapse properties and subsequently for their anti-craving action.     

Trigeminal denervation and operant behavior in the rat.

39 male Wistar rats underwent selective sectioning of trigeminal sensory and motor nerves in 2 experiments to examine the contribution of the sensorimotor system to the control of instrumental responses reinforced with food or water. It was hypothesized that trigeminal denervation would disrupt motivational systems mediating Ss' thirst and hunger. Results show that unilateral sectioning of either Section V sensory or V motor nerves had no significant effect on leverpressing. Bilateral sectioning significantly reduced leverpressing, and the deficit was greatest in Ss with trigeminal motor nerve sectioning. It is concluded that trigeminal orosensory or oromotor denervation disrupts performance on a food- or water-reinforced task in which execution does not require a trigeminally mediated response. Findings are discussed in terms of motivational and reinforcement accounts of instrumental learning. (32 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Reversal of H-reflex operant conditioning in the rat

After developing a rapid gel filtration method to prepare pure and stable apoenzyme forms of D-amino acid oxidase from the yeast Rhodotorula gracilis, we carried out comparative kinetic studies on the reconstitution to holoenzyme (with FAD) of the intact (40 kDa) and proteolyzed (38.3 kDa) apoenzyme forms of this oxidase. Changes in catalytic activity and flavin and protein fluorescence revealed that in both cases reconstitution was biphasic. The proteolyzed enzyme was catalytically competent, but unlike the intact form was unable to dimerize following formation of the apoprotein-FAD complex. We present evidence that reconstitution of holoenzyme from apoenzyme plus FAD does not involve dimerization, and that dimerization is not necessary for expression of DAAO activity. We propose that both apoenzyme forms share a common reconstitution mechanism, which includes a step of conformational interconversion of an enzymatically active intermediate to the final holoenzyme.     

Cocaine self-administration under conditions of restricted and unrestricted food access.

Four rhesus monkeys (Macaca mulatta), maintained at reduced body weight and restricted food availability, had access to a 0.8-mg/ml cocaine solution and vehicle under a concurrent fixed-ratio (FR) 8 schedule. Over days, the cocaine concentration was reduced (0.57, 0.4, 0.2, 0.1, 0.05, 0.025) and then returned, gradually over days, to 0.8 mg/ml. The ratio value was then varied (to 16, 32, 64, 128, and 8). Food access was unrestricted, and the ratio and the concentration manipulations were then repeated. During food restriction cocaine served as a reinforcer for all monkeys, whereas during free feeding cocaine functioned as a reinforcer for 3 of 4 monkeys; with these monkeys, the dose-response curve obtained under free feeding was shifted to the right of that obtained under food restriction. There were no differences in FR response curves obtained during food restriction and unrestricted feeding. These data suggest that food restriction increases cocaine's reinforcing effects and that the higher the cocaine dose, the greater are the reinforcing effects. A demand curve analysis was completed, and data are discussed in terms of microeconomic principles. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Genomic screen for QTLs underlying alcohol consumption in the P and NP rat lines

PURPOSE: We examined the effects of human urine on the adhesion of calcium oxalate monohydrate (COM) crystals to Madin-Darby canine kidney (MDCK) cells in vitro. METHODS: Quantitative assay of COM crystal adhesion to MDCK cells: MDCK cells were exposed to COM crystal suspension for 5 minutes. Various urine samples were added in the COM crystal suspension. The adherent COM crystals on the MDCK cells were dissolved by 5 N hydrochloric acid. Calcium concentration of the solution was measured by atomic absorption analysis to quantify the volume of adherent COM crystals. This assay was applied for the experiments as follows. (1) Effect of human urine on COM crystal adhesion. (2) To investigate whether human urine inhibited COM crystal adhesion by acting on the crystal surface or on the cell surface. (3) Isolation of the substance from human urine that inhibits COM crystal adhesion. (4) Comparison of the inhibitory activities of the urine between from stone formers and healthy controls. RESULTS AND CONCLUSION: (1) Human urine had a strong inhibitory effect on COM crystal adhesion to MDCK cells. (2) The capacity of human urine to inhibit adhesion of COM crystals to MDCK cells was shown to be mediated by their ability to act on the crystal surface. (3) We isolated a macromolecular fraction (MW 60,000) that had strong capacity to inhibit cellular adhesion of COM crystals through ion exchange and gel filtration chromatography. (4) Nine urine samples from stone formers demonstrated extreme low inhibitory activities, which supposed us that the inhibitory capacity of the urine against crystal adhesion might be one of the risk factors in kidney stone formation.     

Septal influences on operant responding in the rat.

In 3 experiments with a total of 74 male albino Sprague-Dawley rats, the afferent and efferent connections of the septum with the hippocampus (fornix) or with the hypothalamus and lower brain stem (medial forebrain bundle) were transected by means of an encephalotome near the point where these pathways enter or leave the septal area. A transection of the fornix that produced minimal direct damage to cellular components of the septum or hippocampus reproduced the effects of large septal lesions on responding in several temporally defined paradigms that involve periods of response suppression (DRL, discriminated Sidman avoidance, FI). Transection of the medial forebrain bundle fibers that interconnect the septum with the hypothalamus and lower brain stem did not affect behavior in any of these paradigms. It is suggested that these observations be viewed in the context of the results of earlier investigations by the authors (see record 1974-27002-001), R. J. Carey (see record 1969-13784-001), and J. M. McDougall et al (see record 1969-13791-001), which showed that transection of the medial forebrain bundle reproduces several other components of the septal lesion syndrome. (28 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sodium balance of hyper- and hypo-natriophilic rats under basal conditions and during sodium deprivation

Sodium and water balance was determined in two strains of Wistar rats selectively bred for high (hypernatriophilic, HR) or low salt preference (hyponatriophilic, HO) under basal conditions and during sodium deprivation. Male rats from each stain were selected for an average ingestion of 1.5% NaCl solution of more than (HR) or less than (HO) 4 ml 100 g body weight (-1) day (-1), during a 10-day period. HR rats (N = 17) presented markedly higher sodium intake under basal conditions (2.983 +/- 0.316 mEq 100 g body weight (-1) day (-1)) than HO rats (N = 12; 0.406 +/- 0.076 mEq 100 g body weight (-1) day (-1); Mann-Whitney test, P < 0.01). Water (HR: 8.6 +/- 0.57; HO: 7.7 +/- 0.32 ml 100 g body weight (-1) day (-1)) and sodium balances (HR: 0.936 +/- 0.153; HO: 0.873 +/- 0.078 mEq 100 g body weight (-1) day (-1)) were similar in both strains, despite a higher sodium and total fluid (HR: 16.3 +/- 1.06; HO: 10.8 +/- 0.49 ml 100 g body weight (-1) day (-1); P < 0.01) ingestion in HR rats. During sodium deprivation HR rats (N = 13) exhibited a sodium balance similar to that of HO rats (N = 13) (HR: -0.159 +/- 0.011; HO: -0.129 +/- 0.019 mEq 100 g body weight (-1) day (-1)), and, in addition, an adequate suppression of natriuresis (HR: 0.049 +/- 0.011; HO: 0.026 +/- 0.004 mEq 100 g body weight (-1) day (-1)). These data show that HR rats present hypernatriophilia as a primary trait, since their sodium-conserving mechanisms are intact. Therefore, these rats provide an adequate model to study factors that determine innate sodium preference.     

A physiological effect of cognitive dissonance under stress and deprivation.

An experiment and a partial replication were conducted to relate the change of motivation due to dissonance reduction and commitment to physiological changes. The experimental technique was based on food deprivation studies by Brehm which showed that already deprived individuals who committed themselves to further fasting under conditions of low reward decreased their self-estimates of hunger, while the reverse was true for those given high rewards. The data suggest that a person who has convinced himself that he is not so hungry tends to respond physiologically as if he were not hungry. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effect of substance P on collagen concentration in rat colon

Anastomotic leakage is the main reason of high mortality in colorectal surgery. The healing of anastomosis is predominantly derived from collagen fibrils. Substance P causes the proliferation of fibroblasts and connective tissue. The effect of SP on postoperative changes of collagen concentration was measured around the anastomotic side in rats. The studies shows, that SP induces a significant decrease in collagen synthesis in colon.     

The effect of light deprivation on the mouse lens

This work was undertaken to test the hypothesis that first exposure of the eye to light is responsible for the changes in lens protein expression patterns observed around the time of birth. The effect of light deprivation on lens properties was examined in Balb c mice which were bred, reared and maintained in complete darkness for up to 7 months. Data were collected on body weight, lens weight, lens protein contents and crystallin distributions. The data were compared with those obtained from age matched mice maintained in natural light/dark conditions. No significant differences were observed in body weight between animals maintained in the light and dark. However, animals kept in the dark had significantly smaller lenses. After 6 months in the dark, the lens represented 0.02% of body weight compared with 0.031% in the light reared animals (P < 0.001). Lens protein concentration, insoluble protein contents and crystallin synthesis patterns were indistinguishable for the two groups of animals. It is concluded that light stimulation of the eye is required for optimal lens growth but does not affect the production of specific crystallins.     

Anticipatory cues can interfere with inhibitory operant behavior in the rat

In four separate experiments a total of 24 male rats were trained for 30 min. daily in the same temporal order to inhibit their responses for at least 6 sec. before a response-contingent reward was delivered (DRL-6 sec.). The rats tested as the second group each day displayed about twice the number of errors (effect size = 40%) shown by rats tested in the first or third groups. These results suggest that anticipatory cues, acquired within two sessions, interfere with response inhibition during an appetitive task for a limited time (between a few minutes to about one hour). The results are consistent with the hypothesis that learned anticipation of reward may decrease inhibitory mechanisms by facilitating limbic lability.     

Self-licking deprivation and maternal behaviour in the primiparous rat.

Self-licking and/or collar licking was prevented in 25 female rats from the 21st day of age by means of a rubber collar about the neck. The ability of these Ss to deliver and maintain their litters did not differ from that of those whose collars did not restrict licking or from that of uncollared controls. This questions the hypothesis that preparturitive self-licking behavior is important for normal parturition and maternal behavior. (French summary) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Technics and methods of intravital microangiography in the rat lung under conditions of shock

Report on a method of opacifying the pulmonary terminal blood stream track in normal animals and those with experimentally induced tourniquet-shock. Based on own experiences from more than than 200 experimental animals (rats) material, technique, and method are described in detail, and some important errors are discussed that might arise and should be avoided.     

Social deprivation and stimulus satiation in the albino rat.

Conducted 2 experiments, with a total of 288 male Sprague-Dawley albino rats, to explore the mechanisms whereby social deprivation leads to increased sociability in rats. Exp I housed Ss alone or in pairs with additional nonsocial stimulation, with additional response opportunities, or with no added social surrogates for 3 wks prior to testing for sociability. Social deprivation led to a strong increase in sociability, and this was not ameliorated by stimulus or response enrichment. Exp II exposed alone or pair-housed Ss to handling, human contact, or no stimulation and found that human exposure did serve a social surrogate function. This result suggests that sociability in rats represents to some degree a search for complex and unpredictable stimulation. (25 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)