Alcohol Intake In Rats Research Articles

Ultrasonic Vocalization Behavior Differs Between Lines of Ethanol‐Preferring and Nonpreferring Rats

To further understand the relationship between emotional state and alcohol intake in rats, the tendency to emit ultrasonic vocalizations in response to an aversive, but nonpainful, air puff stimulus was tested in several rat lines. Included in this group were Maudsley Reactive (MR) and Non-Reactive (MNR) rats, and several lines of rats with either high ethanol preference or a low ethanol preference: Preferring, (P), Alko-Alcohol (AA), and Fawn-Hooded (FH) animals; and Non-Preferring (NP), Alko-Non-Alcohol (ANA), and Flinders Resistant Line (FRL). MR rats emitted fewer ultrasonic vocalizations (USVs) and showed less preference for ethanol than did MNR animals. An overall analysis that included the P, NP, FH, FRL, AA, and ANA groups demonstrated a significant negative correlation between the total number of USVs emitted and ethanol consumption. NP, FRL, and especially ANA rats (low ethanol-preferring) emitted the most USVs--to an extent similar to that typically found for normal rats. The duration of vocalizing was higher only in the NP and the FRL rats the relative to their P and FH comparison groups, respectively. In the ethanol-preferring and nonpreferring lines, the numbers of USVs emitted correlated positively with the duration of vocalizing, but not with the latency to vocalize, which in turn did not correlate strongly with ethanol intake. The latency to vocalize did not correlate significantly with ethanol intake across all drinking lines or MR or MNR rats, but was found to be higher in FH and AA rats relative to their nondrinking comparison groups. These associations suggest that the relationship between emotional state and ethanol drinking is complex and cannot be attributed to a simple elevated state of anxiety or emotionality. Further examination of the central nervous system mechanisms mediating the difference in USVs between paired lines of ethanol-preferring and nonpreferring rats may identify neurochemical factors that predict ethanol preference.

Ultrasonic Vocalization Behavior Differs Between Lines of Ethanol-Preferring and Nonpreferring Rats

To further understand the relationship between emotional state and alcohol intake in rats, the tendency to emit ultrasonic vocalizations in response to an aversive, but nonpainful, air puff stimulus was tested in several rat lines. Included in this group were Maudsley Reactive (MR) and Non-Reactive (MNR) rats, and several lines of rats with either high ethanol preference or a low ethanol preference: Preferring, (P), Alko-Alcohol (AA), and Fawn-Hooded (FH) animals; and Non-Preferring (NP), Alko-Non-Alcohol (ANA), and Flinders Resistant Line (FRL). MR rats emitted fewer ultrasonic vocalizations (USVs) and showed less preference for ethanol than did MNR animals. An overall analysis that included the P, NP, FH, FRL, AA, and ANA groups demonstrated a significant negative correlation between the total number of USVs emitted and ethanol consumption. NP, FRL, and especially ANA rats (low ethanol-preferring) emitted the most USVs—to an extent similar to that typically found for normal rats. The duration of vocalizing was higher only in the NP and the FRL rats the relative to their P and FH comparison groups, respectively. In the ethanol-preferring and nonpreferring lines, the numbers of USVs emitted correlated positively with the duration of vocalizing, but not with the latency to vocalize, which in turn did not correlate strongly with ethanol intake. The latency to vocalize did not correlate significantly with ethanol intake across all drinking lines or MR or MNR rats, but was found to be higher in FH and AA rats relative to their nondrinking comparison groups. These associations suggest that the relationship between emotional state and ethanol drinking is complex and cannot be attributed to a simple elevated state of anxiety or emotionality. Further examination of the central nervous system mechanisms mediating the difference in USVs between paired lines of ethanol—preferring and nonpreferring rats may identify neurochemical factors that predict ethanol preference.

Effects of early weaning and social isolation on subsequent alcohol intake in rats

The present study investigated the influence of early weaning and separation from mother and littermates on voluntary ethanol intake and general activity during prepuberal age, and adult age corticosterone levels. On day 16 after birth the male offspring of a litter were divided in three groups, each subjected to a different rearing condition: 1) early weaned and isolated from its littermates; 2) early weaned but growing up together with two littermates; 3) staying with mother and two littermates. On day 25 the animals were tested for general activity including assessment of fearfulness. From day 30 all animals were given a free choice between water and ethanol solution. The ethanol concentration was increased by 2% during each of the following weeks until 10% was reached during the 5th week. Ten days later, after cessation of alcohol testing, blood samples were taken from the tail for assessment of plasma levels corticosterone. The isolated, early weaning pups displayed higher activity levels than both normally reared pups and group-living, early weaning pups. The quotient peripheral locomotion/total locomotion was lower for the isolated pups compared with the other groups, suggesting less fearfulness in the early weaned, isolated pups. For 2%, 4%, and 6% ethanol solutions the normal-reared rats consumed more ethanol and displayed higher ethanol preference than either of the early weaned groups of animals. No group differences were observed either at 8% or 10% ethanol solutions. Levels of plasma corticosterone in adult age in the early weaned rats were slightly reduced, not reaching statistical significance, compared to the normally weaned animals.

The delta 2-opioid receptor antagonist naltriben selectively attenuates alcohol intake in rats bred for alcohol preference

The relative importance of different opioid receptor types in mediating alcohol drinking behavior compared with the intake of other ingesta can be determined by characterizing the effects of selective opioid antagonists on the intake of various ingesta. Nonselective opioid receptor antagonists suppress the intake of many ingesta including alcohol, food, water, and sweets. Two distinct subtypes of delta-opioid receptors, delta 1 and delta 2, have recently been identified in rodent brain. We have previously reported that naltrindole (NTI), which blocks both delta 1 and delta 2 receptors, suppresses both alcohol and saccharin intake in rats selectively bred for high alcohol preference (P line). We now report that naltriben (NTB), an opioid antagonist that is selective for delta 2-opioid receptors, suppresses alcohol intake in rats of the P Une and the effect appears to be both specific for alcohol and independent of alcohol palatability. NTB may reduce alcohol intake by attenuating the reinforcing pharmacological properties of alcohol.

Further evidence that 5-HT 4 receptor antagonists suppress alcohol intake in rats

Further evidence that 5-HT 4 receptor antagonists suppress alcohol intake in rats

Voluntary Alcohol Consumption During Pregnancy in Fawn-Hooded Rats Induces Behavioral Deficits in Offspring

Most previous studies on the effects of prenatal alcohol exposure have involved the forced intake of alcohol in rats which do not voluntarily drink alcohol. Because the Fawn-Hooded rats voluntarily drink substantial quantities of alcohol (6-8 g/kg), the present study examined the consequences of such high voluntary intake of alcohol on the offspring. Female rats were screened for alcohol intake and then mated with males. The males were removed 5 days later and two females were presented with two bottles - one containing tap water and the other alcohol (10%, v/v) throughout pregnancy and until the offspring were 10 days old. Another two females received tap water throughout the experiment. A battery of behavioral tests was conducted when the rats reached 70 days of age. The offspring of alcohol-exposed mothers tended to be hyperactive in the open field, especially for grooming. The alcohol-exposed offspring also spent less time in the open arms of an elevated plus maze, suggesting a high level of anxiety, and were more immobile in the forced swim test, suggesting a high level of depression. These findings are comparable to those found previously in Russia by Trofimov and Smolnikova following forced alcohol exposure. Further studies of prenatally alcohol-exposed Fawn-Hooded rats may be informative.

Ritanserin and voluntary alcohol intake in rats.

In a previous study (Rammsayer & Vogel, 1991), rats selectively bred for high and low catecholamine responses to stress showed a selective response to the 5-HT2 receptor blocker ritanserin. However, it remained unclear whether selective breeding resulted in a decrease in 5-HT responsivity, as suggested by the lack of an effect in high stress responding rats, or in an increase in 5-HT responsivity, as suggested by ritanserin-induced reduction in alcohol intake in low-responding rats. To answer this question, nonselectively bred rats were forced to drink a 5% alcohol solution for 10 days. For the subsequent six days, animals were injected subcutaneously with 2.5 mg/kg/2 ml ritanserin or vehicle only, and both a 5% solution of alcohol and water were presented to the animals. Ritanserin neither affected alcohol nor total fluid intake suggesting that in the general population of N/NIH (Hansen) rats as well as in rats of the same strain selectively bred for high catecholamine responses, mesolimbic dopaminergic activity is not effectively modulated by specific blockade of 5-HT2 receptors. However, a very pronounced ritanserin induced difference in daily water intake between nonbred male and female rats became evident.

Influence of the 5-HT 1A receptor agonist ipsapirone on voluntary alcohol intake in rats

The effect of the azapirone derivative ipsapirone on anxiety and the free-choice consumption of alcohol was studied in male rats. Animals were housed three in a cage with a different composition each day to increase anxiety. The animals were offered a two-bottle free choice consumption of tap water or a 5% ethanol solution. Ipsapirone was given in the drinking fluid daily at about 10 mg/kg per day. As expected, social unstable groups exhibited a higher level of anxiety as compared to social stable groups. Ipsapirone reduced significantly the anxiety in the unstable group. Pretreatment with ipsapirone before alcohol exposure resulted in a marked decrease of subsequent ethanol intake by about 45% as compared to drug free control animals. Administration of the drug to rats already drinking alcohol showed a similar decrease of ethanol intake by about 50%. These results indicate that the relatively specific 5-HT 1A receptor agonist ipsapirone, given orally, reduces anxiety as well as alcohol initiation or maintenance in rats.

Amperozide, a 5-HT 2 antagonist, attenuates craving for cocaine by rats

Amperozide, a novel 5-HT 2 receptor antagonist with little affinity for the dopamine receptor, suppresses the intake of alcohol in rats without affecting food intake or inducing other side effects. Because of these actions, amperozide was examined for its efficacy on the oral preference by the rat for a solution of cocaine. In this study, rats were selected for their voluntary consumption of at least 10 mg/kg of cocaine per day in a two-choice paradigm. A solution of 0.02% to 0.06% cocaine plus 0.03% saccharin in water was offered to each animal simultaneously with a solution of only 0.03% saccharin in water. The consumption of food and both fluids, as well as body weight, was recorded daily for three successive periods: 4 days of pretreatment baseline; 3 days during injections of either amperozide or the saline vehicle solution; and 4 days postinjections. Amperozide was administered SC twice daily in a dose of 0.5, 1.0, or 2.5 mg/kg. The volitional intake of cocaine was significantly reduced not only during the 3-day period of injections of amperozide but also during the 4-day posttreatment period. Amperozide exerted little or no effect on the intake of food or on body weight. Radioligand binding experiments confirmed that amperozide has at least a twentyfold greater affinity for 5-HT 2 receptors in the frontal cortex of the rat, as compared to striatal DA 1 and DA 2 receptors, with the proportion value similar to that of the 5-HT 2 receptor antagonist, ritanserin. It is concluded, therefore that amperozide, which produces little or no adverse side effects, appears to be potentially useful for the treatment of the addiction to cocaine.

Captopril and hydrochlorothiazide (Capozide) combine to enhance the reduction in voluntary alcohol intake in rats.

The effect of Capozide, the combination of captopril with a hydrochlorothiazide diuretic, on voluntary alcohol intake was assessed in two experiments. In experiment 1 naive rats who were maintained on ad libitum food and water were given daily 40-min access to a 6% (w/v) alcohol solution and water. Daily intraperitoneal injections of captopril (10 mg/kg) reduced alcohol intake, but the combination of captopril (5 and 10 mg/kg) and hydrochlorothiazide (2.5, 5, and 10 mg/kg) enhanced the reduction in intake. In experiment 2, captopril alone, hydrochlorothiazide alone, and the combination of captopril and hydrochlorothiazide were again administered daily in the limited access procedure. Captopril (10 mg/kg) again reduced alcohol intake as did all three doses of hydrochlorothiazide (2.5, 5, and 10 mg/kg). Compared with the individual effects of captopril and hydrochlorothiazide, Capozide exerted a supra-additive reduction in alcohol intake. These effects were not due to drug-induced changes in the pharmacokinetics of alcohol. Taken together these results demonstrate an enhanced potency of Capozide in suppressing alcohol intake and invite their testing in a population of hypertensive alcoholics and alcohol abusers.

Suppression of alcohol preference in rats induced by risperidone, a serotonin 5-HT 2 and dopamine D 2 receptor antagonist

The present study investigated the effect of the 5-HT 2 and dopamine D 2 receptor antagonist risperidone on alcohol preference in the rat. Rats with developed preference for 3% ethanol were injected subcutaneously (SC) with 10, 1, or 0.1 mg/kg of risperidone for 7, 10, and 10 days, respectively. Risperidone (10 mg/kg) evoked an inhibitory effect on alcohol preference similar (rapid onset, but short duration) to that observed after treatment with the dopamine D 2 receptor antagonist haloperidol, 0.0625 mg/kg, SC. The lowest dose of risperidone (0.1 mg/kg) evoked marked inhibition of ethanol drinking, similar (slow onset, but long-lasting effect) to that produced by the 5-HT 2 receptor antagonist ritanserin, 1 mg/kg, SC. Present results demonstrate that risperidone suppresses alcohol preference in the rat and suggest that its effect, depending on the dose, might involve different neurochemical mechanisms (mainly dopaminergic at high doses and mainly serotonergic at low doses). The results obtained with the lowest dose of risperidone (0.1 mg/kg), at which the drug is rather selective for 5-HT 2 receptors, are in keeping with previous findings obtained with ritanserin and support the hypothesis that 5-HT 2 receptor blockade reduces alcohol intake in rats.

Neonatal administration of a GABA-T inhibitor alters central GABAA receptor mechanisms and alcohol drinking in adult rats.

Long-term effects of chronic treatment with a GABA-T (GABA-transaminase) inhibitor, ethanolamine O-sulphate (EOS) (200 mg/kg/day for the postnatal days 3-21) on the binding parameters of GABAA receptors, hypothalamic monoamines and subsequent behavior were studied in Wistar rats. At the age of 1 month, EOS-treated rats showed reduced activity in the open-field and, at the age of 4 months, their voluntary alcohol consumption was increased. No changes were seen in Porsolt's swim test or in the plus-maze test. Weight gain was significantly retarded in EOS-treated rats. Maximal stimulation of [3H] flunitrazepam binding by GABA was decreased in the cerebral cortex and the EC50-value for the GABA stimulation increased in the hippocampus in the EOS rats at the age of 4 months. EOS treatment did not alter the cerebellar diazepam sensitive and insensitive binding components of the imidazobenzodiazepine [3H]Ro 15-4513. No changes were observed in the hypothalamic monoamine concentrations. The results are in agreement with the idea that GABA-T inhibitor treatment permanently alters GABAA mechanisms. Moreover, altering the CNS GABA level during development increases adult alcohol intake in rat.

The relationship between saccharin and alcohol intake in rats

Male rats were given daily sessions during which a palatable saccharin solution was available. Based on intakes averaged over 3 days, groups with low, intermediate, or high intake of saccharin were formed. These rats were then given daily sessions in which alcohol (2–8%) or water were available. Initially, sessions were conducted with rats on a food restriction schedule; in later sessions, food was available ad lib. When rats were food restricted, there were no differences among the groups in terms of alcohol or water intake. When the food restriction schedule was discontinued, alcohol intake in the intermediate and high saccharin intake groups was generally higher than that of the low saccharin group. On the final series of alcohol sessions, the high saccharin group consumed significantly more 2% and 6% alcohol than the low saccharin group. These results are consistent with reports which have found that rats selected for high or low alcohol intake have corresponding high and low intakes of saccharin.

Differential effects of a 5-HT2 receptor blocker on alcohol intake in rats selectively bred for high and low catecholamine responses to stress

The effect of the selective 5-HT2 receptor blocker ritanserin on alcohol consumption was investigated in two strains of rats selectively bred for high and low catecholamine responses to stress. Rats were forced to drink a 5% alcohol solution for 10 days. For the subsequent six days, animals were injected subcutaneously with 2.5 mg/kg/2 ml ritanserin or vehicle only, and both a 5% solution of alcohol and water were presented to the animals. Ritanserin affected neither water nor total fluid intake. Furthermore, no effect of ritanserin on alcohol consumption could be demonstrated in high-responding rats, whereas in low-responding rats a very pronounced ritanserin-induced reduction in alcohol intake was observed. Results are discussed in terms of mediating effects of serotonergic neurons on mesolimbic dopaminergic reward systems related to drug addiction.

Cholecystokinin-induced satiation with ethanol: effects of lighting cycle and limited access procedures

Cholecystokinin (CCK) is a brain-gut neuropeptide and hormone previously shown to inhibit alcohol intake in water- or food-deprived rats. The effects of CCK and the phase of lighting cycle on alcohol intake in rats were investigated in a comparison of limited access and water-restriction procedures. The limited access procedure (LAP) is a recently developed technique for inducing free-choice alcohol consumption in nondeprived animals. Two groups of 12 male rats each were maintained in either normal or reversed 12:12 L:D lighting cycles and simultaneously given 40 minutes' access to 6% w/v ethanol and water in nonhome cages. After adaptation to this procedure, CCK octapeptide (0.5-16 micrograms/kg) was injected IP prior to access to fluids. During LAP, CCK reduced alcohol intake and increased water intake more potently in the dark phase. These effects of CCK were more reliable when the design was replicated, which suggests the importance of acquired expectancies for the development of CCK's actions. CCK more effectively reduced alcohol intake in LAP, than in a 23.3-h water-deprivation procedure for inducing alcohol intake in a 2-bottle choice test with water. However, CCK was less so effective in LAP, than in the water-deprivation procedure when alcohol was presented alone in a 1-bottle test. The alcohol satiation effect of CCK is independent of prior deprivation and not an artifact of thirst reduction, debilitation, or conditioned aversion, because CCK strongly increased water intake in the limited access procedure, and ethanol preference remained robust after experience with CCK. CCK may operate endogenously as a specific factor in satiation with ethanol.

Effects of central injection of tachykinins on alcohol intake in rats

Subcutaneous pretreatment of rats with neurokinin (NK) A or the fragment NKA(4–10) reduced the degree of gastric lesions induced by oral administration of 96% ethanol. The protective effect of NKA(4–10) was dose-dependent. Arg-NKB, the water soluble derivative of NKB, was less effective than NKA or NKA(4–10) while [Me-Phe7]NKB, substance P (SP) and SP-methyl-ester were inactive. The NKA(4–10) antilesion effect was reversed by pretreatment with N-ethyl-maleimide, suggesting a possible involvement of sulphydryls in its action. Among the nonmammalian tachykinins, kassinin significantly reduced ethanol-induced lesions while eledoisin and physalaemin at equivalent molar doses were inactive. These results provide, for the first time, evidence that tachykinins and their derivatives exert gastroprotective activity toward ethanol-induced haemorragic lesions. Assuming a receptor-mediated mechanism, NK-2 sites could be involved.

Angiotensin Converting Enzyme Inhibitors Reduce Alcohol Consumption: Some Possible Mechanisms and Important Conditions for Its Therapeutic Use

Alcoholism is a prevalent problem of contemporary society, yet there are virtually no clinically effective drugs for the management of this disorder. A previous study demonstrating the ability of angiotensin-converting enzyme (ACE) inhibitors to attenuate voluntary alcohol intake in rats prompted the suggestion that these drugs, currently marketed for the treatment of hypertension, may also be useful in dealing with human alcohol abuse. The present experiments explored in more detail the effect and possible mechanisms of action of this class of drug on alcohol consumption in rats. Experiment one demonstrated that Abutapril, a new ACE inhibitor, significantly reduced alcohol intake and that this effect could not be blocked by either an ANG II or an opiate receptor antagonist suggesting that neither the peripheral renin-angiotensin system (RAS) nor the endogenous enkephalins are involved in the ability of ACE inhibition to attenuate alcohol intake. Experiments two and three showed that ACE inhibition effectively reduced alcohol drinking faster in animals with elevated RAS activity and not at all in animals with suppressed RAS activity indicating that initial levels of RAS activity may determine the speed and ability of ACE inhibition to attenuate alcohol intake. ACE inhibitors may reduce alcohol intake by elevating a nonapeptide fragment or by elevating central ANG II levels. The assessment of this class of drugs to reduce alcohol intake in humans should include a monitoring of the initial level of activity in the renin-angiotensin system since this may be a predictor of the effectiveness of treatment with the ACE inhibitors.

THE INTERACTION BETWEEN VOLUNTARY ALCOHOL CONSUMPTION AND DIETARY CHOICE

The influence of forced and voluntary alcohol intake on the choice by AA (heavy drinking) and ANA (light drinking) rats between carbohydrate, protein and fat was studied. Alcohol consumption reduced the carbohydrate intake but did not influence the total energy consumption. In AA rats on free choice, voluntary alcohol intake correlated negatively with carbohydrate consumption but positively with protein and water intake. It was also found that the day to day variation in alcohol intake was of the same order as those in carbohydrate, protein and water intake and smaller than that in fat consumption. These findings in addition to earlier observations point to a regulation of alcohol intake in rats which in many respects resembles the regulation of dietary choice.

Effects of unavoidable electric shocks on voluntary alcohol consumption in the rat.

The purpose of this experiment was to study the effects of electric shocks on voluntary alcohol intake in rats. Alcohol intake was measured using individually determined alcohol concentrations. Contrary to many previous studies, alcohol intake was reduced during the stressful treatment. It is concluded that accounting for individual differences in alcohol intake is important when studying the effect of stress on alcohol consumption.

Morphological alterations due to long term alcohol intake in rats

The myocardium and blood vessels of 20 rats kept for one year on DeCarli and Lieber's liquid diet containing alcohol to 36% of total Joules were examined with routine histological, histochemical and electron microscopical methods. No changes in the gross anatomy, histology, histochemistry and electron microscopy of the arteries, veins and capillaries were found. Subcellular damage of the atrial and ventricular myocardial cells was observed. A varying number of mitochondria were affected in each of the animals: degenerated mitochondria, mitochondria with electron lucent matrix, with concentric cristae, of bell shape, with negative succinic dehydrogenase activity or vacuolated mitochondria were found. In 10% the myofibrils, and in 30% the sarcoplasmic reticulum were damaged. Secretion and lipofuscin granules increased in number in 25% of the animals. It is concluded that although the submicroscopic alcoholic alterations are similar to some of those reported in experimental ischaemia, the decrease in myocardial blood flow may not be held solely responsible for the alcoholic damages. A toxic effect of alcohol, acetaldehyde and catecholamine is postulated.