Rat ethanol intake: Suppression by intracranial surgery and facilitation by intracranial stimulation

Implantation of stimulating electrodes into the rat lateral hypothalamus suppressed subsequent home-cage ethanol intake. Lateral hypothalamic stimulation overcame this influence, returning animals to the levels of unimplanted, unstimulated control animals. The effects of surgery were temporary; the implanted control animals reached the intake levels of the stimulated and unimplanted control animals after 60 days of ethanol exposure. Control animals that were given pentobarbital or ether anesthesia without surgical insult drank as much as unimplanted controls.Supported in part by Grant No. R01 MH21850-01 from the United States Public Health. Service and by a grant from the Licensed Beverage Industries.     

Increased alcohol preference in rats following repeated exposures to alcohol

Summary When offered water and different solutions of ethyl alcohol in a freechoice situation, naive rats prefer alcohol at low concentrations but reject alcohol as the concentrations are increased sequentially. Rats which were either group or individually housed and forced to drink a non-preferred 12 or 15 per cent alcohol solution, drank less alcohol than control animals in a subsequent free-choice test. On the other hand, the animals that were repeatedly exposed to 11-day periods during which the concentrations of alcohol were systematically increased from 3 to 30 per cent consumed two to three times more alcohol in the seventh sequence than in the first sequence. In the free-choice situation this acclimation effect occurred when water was constantly present. This method appears to be useful for inducing animals to consume large volumes of ethyl alcohol.This research was supported by NSF Grant GB 7906, ONR contract N 00014-67-A-0226-0003 and by a grant from the Wallace Laboratories. We thank Linda Kwolek, Sue Riley, T. J. Cicero and P. Curzon for their valuable assistance.     

Altered sensitivity to ethanol following prenatal exposure to barbiturate

Female mice (genetically heterogeneous stock) were fed milled mouse food containing 3 g/kg phenobarbital (PhB) and water as their only nutritional source from gestation days 9–18. Control dams received milled food and water. Blood PhB levels of treated females and fetuses were 40–200 g/ml. At the age of 50 days, male offspring were injected with 3.5 g/kg ethanol. Sleep time was monitored and in randomly selected individuals, brain ethanol levels were determined upon awakening. To assess the rate of metabolism in the treated and control offspring, blood ethanol levels were determined in other randomly selected individuals at 60 and 120 min post-injection. Offspring who received PhB prenatally were resistant to the hypnotic effects of ethanol as evidenced by their 33% shorter sleep time compared to controls (P<0.001). The brain ethanol levels upon awakening were higher than control in the offspring born to the barbiturate-treated mothers (P<0.001), indicating that the resistance to ethanol was due to factors residing within the central nervous system.     

Ethanol as a reinforcer for rats: Effects of concurrent access to water and alternate positions of water and ethanol

Water and ethanol solutions were concurrently made available on a continuous reinforcement schedule to 4 food-deprived male albino rats during daily 1-hr sessions in an operant conditioning chamber equipped with 2 levers and 2 liquid dippers. The number of ethanol reinforcements substantially exceeded the number of water reinforcements for each rat at each concentration studied (8, 16, and 32% w/v). Water reinforcements were low in number and did not vary with ethanol concentration. As the ethanol concentration was increased, the number of ethanol reinforcements obtained decreased, while the quantity consumed (mg/100 g of body weight/hr) increased. The highest rate of responding occurred at the beginning of the session.     

Chlordiazepoxide''s interaction with ethanol intake in the rat: Relation to ethanol exposure paradigms

Chlordiazepoxide's interaction with ethanol (5% v/v) intake was assessed in rats on a feeding regimen producing high daily quantities of ethanol intake (schedule-induction procedure with intermittent feeding), more moderate amounts of ethanol intake (a single daily feeding), and small amounts of ethanol intake (free feeding). Six days of twice daily sham injections (IP) were followed by 12 days of 0 (vehicle), 5, 10, or 15 mg/kg (twice daily) chlordiazepoxide, and finally six days of the saline (vehicle) injections. Rats in the intermittent feeding daily consumed 9.9–12.3 g/kg (80–95 ml) of ethanol on baseline which was reduced 15 to 33% by the drug. In the single feed condition most rats were drinking 70 to 85 ml (8.8–10.3 g/kg) of ethanol and this was reduced 15–40% by the drug. During the six days after drug, intake in both of these feeding regimens returned to the baseline level. Ethanol intake of rats under the free feeding condition (48 ml, 3.5 g/kg on average) was not affected by the drug, nor was water intake under any of the three feeding regimens.     

A critical evaluation of tetrahydroisoquinoline induced ethanol preference in rats

It has been reported [30] that certain tetrahydroisoquinoline compounds, especially salsolinol and tetrahydropaveroline (THP) when infused into the lateral ventricle of rats' brains results in increased preference for alcohol solutions. The effect is reported to be long-term, in that animals do not return to baseline drinking even months later. The current report provides a replication of the original experiments and also extension of the work to complete dose-response curves for salsolinol and THP. Generally we have confirmed that rats of the Sprague-Dawley and Long-Evans strains do increase their alcohol intake in response to infused THP or salsolinol and that the effect is long lasting, up to 10 months. Such animals consume less alcohol at concentrations above 20% than below, in contrast to the previous reports where drinking was maintained at high concentrations of alcohol. While the animals will select alcohol in the face of a saccharin choice, they will not drink alcohol adulterated with quinine. We have failed to observe signs of dependence or withdrawal by these techniques and suggest that the original reports of these signs may have been a result of cellular damage caused by the long-term infusions. Additionally we have carried out extensive dose-response experiments with both salsolinol and THP. Doses of THP of 104 nmoles/day were inhibitory to alcohol drinking. We conclude that these compounds do shift these animals preference for alcohol relatively permanently, but not to the point of gross intoxication nor into the highly aversive range of alcohol concentration. We cannot confirm the reports that salsolinol or THP produce withdrawal symptoms when infused.     

Patterns of ethanol and water consumption as a function of restricted ethanol access and feeding condition

Sixteen male albino rats were divided into two groups of eight animals and maintained at either their free-feeding or at 80% of their free-feeding weight. For four animals, access to 8% ethanol was unrestricted, for the remaining four, access was restricted to eight 20-min access periods per day. Mean amounts of ethanol consumed per bout were greater during restricted access than during unrestricted access for food-deprived animals but not for free-feeding animals. Total daily ethanol consumption was greatest when animals were food deprived and access to ethanol unrestricted. Total fluid consumption and the within session distribution of water and ethanol responding were affected by feeding condition. For food-deprived animals, the amount of water consumed per session remained relatively constant. The increase in ethanol consumption over sessions resulted in an increase in total fluid consumption. For the free-feeding animals, increases in ethanol consumption resulted in decreases in water consumption so that total fluid consumption remained constant. In addition, food-deprived animals consumed all their daily water intake at the beginning of each session when food was present. Free-feeding animals consumed water throughout the session.     

Catalase activity measured in rats naive to ethanol correlates with later voluntary ethanol consumption: possible evidence for a biological marker system of ethanol intake

Catalase activity in blood collected from young rats naive to ethanol (65 days) was significantly and positively correlated with later voluntary consumption of ethanol. Catalase activity levels were also correlated with catalase activity in brain and blood sampled after exposure to ethanol. The results obtained in the present study extend and confirm earlier findings (Aragon et al. 1985c) that brain catalase activity and voluntary ethanol intake are unidirectionally and causally related. The results also suggest that brain catalase activity may be part of an enzymatic system controlling the production and elimination of acetaldehyde in brain. This system may be a biological marker system mediating the affinity of organisms to ingest ethanol.     

EEG and ERP response to chronic ethanol exposure in rats

Chronic ethanol exposure has been described in humans to produce a series of long and short term electrophysiological consequences. Interpretation of the electrophysiological findings in human subjects, however, is made difficult due to concomitant factors, such as nutritional status, premorbid functioning and differences in genetic susceptibility to the effects of ethanol. In the present study, electroencephalograms (EEGs) and auditory event related potentials (ERPs) were utilized to explore the short and longer term effects of chronic ethanol exposure in rats. Rats were continuously exposed to ethanol vapors for a period for 1 month. This treatment produced a mean blood ethanol level of 178 ± 13.86 mg%. EEGs and ERPs were subsequently collected at 10 min, 24 h, and 2 weeks following termination of ethanol exposure. Significant changes in the EEGs and ERPs of these rats could be demonstrated. EEG amplitude increases, as quantified by spectral analysis, were most prominent at the 24h time period, perhaps reflecting a state of rebound excitability. EEG responses were normalized in ethanol-treated rats by 2 weeks post-withdrawal. In contrast, reductions in the N1 and P2 amplitudes of the rat ERPs were prominent after chronic ethanol exposure and following 2 weeks withdrawal, suggesting that ethanol may produce some longer term effects on response to ERP stimuli. Taken together, these studies suggest that ethanol may produce differential effects on EEG and ERPs and that this model may provide a useful substrate for the evaluation of the mechanisms underlying the effects of chronic ethanol exposure.     

Induction of high voluntary ethanol intake in dependent rats

The experimental conditions under which oral high intake may be induced in previously intoxicated rats have been investigated. Seventeen rats were administered intragastrically with 10 g/kg/day of ethanol for 15 days. At cessation of treatment, they were presented a single bottle of alcoholic solution (10% v/v) during 24 hr. For the following 6 days, they received either an ethyl alcohol solution or water in alternation for 8 hours each. Ethanol treated rats exhibited a high oral intake of ethanol equivalent to the previously injected doses. Controls displayed a significantly lower intake of ethanol. It is concluded that the suppression of the withdrawal state by an initial priming oral intake of ethanol in physically dependent rats is a condition for the development of a conditioned taste preference for ethanol as a basis for the behavioral dependence.     

Effect of amygdaloid lesions on ethanol intake in rats

The effect of electrolytic lesions of the amygdala on ethanol intake in ethanol naïve rats has been studied. Rats with basolateral nuclei and lateral nuclei lesions showed a reduced neophobic response to an ethanol solution. However, the ethanol intake was too small in normal and lesioned rats to augment aversion through conditioning. Oral intake of ethanol supplemented by intraperitoneal ethanol injection to reach 2 g/kg indeed enhanced the initial sensory aversion to ethanol. This induced aversion was attenuated after basolateral lesions. An initial aversion to a mixed ethanol-sucrose solution was abolished after basolateral lesions, while the lateral lesions induced an initial preference for this solution. The initial oral intake of ethanol-sucrose in normal rats was again too small to induce the conditioned taste aversion (C.T.A.). Despite the high oral intake of this solution, rats with basolateral lesions did not show a conditioned aversion while laterally lesioned rats exhibited a strong conditioned aversion to the ethanol-sucrose mixture. The results which confirm the suppression of the C.T.A. by basolateral amygdala lesions are discussed in relation to the role of toxicophobia in ethanol intake by rats.     

Voluntary wheel running attenuates ethanol withdrawal-induced increases in seizure susceptibility in male and female rats

We recently found that voluntary wheel running attenuated ethanol withdrawal-induced increased susceptibility to chemoconvulsant-induced seizures in male rats. Since female rats recover from ethanol withdrawal (EW) more quickly than male rats across several behavioral measures, this study was designed to determine whether the effects of exercise on EW seizures also exhibited sex differences. Animals were maintained under no-wheel, locked-wheel or free-wheel conditions and ethanol was administered by liquid diet for 14 days with control animals pair-fed an isocaloric diet, after which seizure thresholds were determined at 1 day or 3 days of EW. Consistent with previous reports, females ran significantly more than males, regardless of diet condition. Introduction of the ethanol-containing liquid diet dramatically increased running for females during the day (rest) phase, with little impact on night phase activity. Consistent with previous reports, EW increased seizure susceptibility at 1 day in non-exercising males and females and at 3 days in males. These effects were attenuated by access to running wheels in both sexes. We also assessed the effects of sex, ethanol diet and exercise on ethanol clearance following an acute ethanol administration at 1 day EW in a separate set of animals. Blood ethanol concentrations at 30 min post-injection were lower in males, ethanol-exposed animals, and runners, but no interactions among these factors were detected. Interestingly, females displayed more rapid ethanol clearance than males and there were no effects of either diet or wheel access on clearance rates. Taken together, these data suggest that voluntary wheel running during ethanol administration provides protective effects against EW seizures in both males and females. This effect may be mediated, in part, in male, but not in female rat, by effects of exercise on early pharmacokinetic contributions. This supports the idea that encouraging alcoholics to exercise may benefit their recovery.     

Effects of phenobarbital on ethanol intake in fluid deprived rats.

Every third day animals were offered either 3 or 7 percent ethanol in place of water during the 1 hr drinking session. Three doses of sodium phenobarbital were administered subcutaneously to 3 groups of animals - 20, 40, and 60 mg/kg. Results indicate that the drug indreases ethavol consumption following the injection but decreases consumption of ethanol on subsequent postdrug days. There was an attenuation in these effects from the first to the third injection. Although a dose effect was not determined, changes in ethanol consumption were greater with the higher concentrations.     

Effect of exposure to high concentrations of toluene on ethanol preference of laboratory rats

Male and female Holtzman Sprague Dawley rats were given 10-minute exposures to high concentrations of toluene twice a week at 10–30 days of age. The rate of acquisition of ethanol preference for these rats did not differ significantly from litter-mate sham exposed controls. Once ethanol preference curves were established, the rats were exposed daily over a 5-day period to high concentrations of toluene. An increase in ethanol intake occurred in most of the rats irrespective of early toluene exposures at 10–30 days of age.     

Consumption of intoxicating beverages by rats and mice exhibiting high and low preferences for ethanol

Lines of rats selectively bred for alcohol consumption or avoidance (AA and ANA, ALKO, Finland) as well as inbred strains of mice (C57/BL/6J and DBA/2J) and common female Wistar rats (Charles River) exhibiting high and low preferences for ethanol were tested under free-choice conditions for their consumption of solutions of ethanol (5, 10, or 15 g/100 ml tap water), sodium pentobarbital (0.19, 0.038, 0.076 g/100 ml tap water), and different beverages containing ethanol in the range of 8.1–9.6% (red and white wine, Scotch, ethanol in Hawaiian Punch). The Wistar rats and the mice classified as alcohol-preferring also tended to consume more of the pentobarbital solution than did alcohol-avoiding animals. Alcohol-nonaccepting (ANA) rats, however, consumed considerably more of all three pentobarbital solutions than did the alcohol-accepting (AA) rats. The intake of pentobarbital by the ANA rats and C57/BL/6J mice was in the range of 25–40 mg/kg/day, quantities that might be expected to produce pharmacological effects discriminable by those animals. The intake of ethanol by ANA rats was markedly elevated when the ethanol was contained in white wine or in punch.     

Relationship between initial sensitivity to ethanol and the high alcohol intake in dependent rats

The high spontaneous intake of ethanol, which can be induced in rats after a period of forced administration, may be used to study the altered state created in the C.N.S. by the chronic exposure to ethanol. The relationship between the initial acute sensitivity to ethanol and this induced high oral intake has been examined in rats. Initial sensitivity was determined in two groups of rats either by a test of motor impairment or by alcohol induced hypothermia. After 15 days of daily IG administration of 10 g/kg, rats were submitted to the ethanol presentations which display the high voluntary intake. Two groups of controls were initially tested for their motor impairment or hypothermia respectively under ethanol and then treated for 15 days with saline injections. The results indicate a highly significant negative correlation between initial sensitivity and the level of dependence induced by a chronic treatment and manifested by a voluntary high intake. In control groups, the low intake of ethanol observed in the final test was not correlated to the initial sensitivity to ethanol as tested by hypothermia but weakly correlated to sensitivity measured by motor impairment. The results are discussed in terms of mechanisms which determine the voluntary intake of ethanol in ethanol naive and dependent rats.     

Memory impairment following combined exposure to delta(9)-tetrahydrocannabinol and ethanol in rats

Cannabis derivatives and alcohol are widely co-abused, particularly among adolescents. Since both ethanol and cannabinoids are known to impair learning and memory, the present study investigated in rats the effects of combined exposure to ethanol and delta(9)-tetrahydrocannabinol (THC) in a memory task, the object recognition test. The results of the present study provide evidence that ethanol, voluntarily ingested in alcohol-preferring rats, and THC, given by intraperitoneal injection, have a synergic action to impair object recognition, when a 15-min interval was adopted between the sample phase and the choice phase of the test. Neither voluntary ethanol ingestion nor 2 or 5 mg/kg of THC were able per se to modify object recognition in these experimental conditions, but when voluntary ethanol ingestion was combined with administration of these doses of THC object recognition was markedly impaired. THC impaired object recognition only at the dose of 10 mg/kg, when its administration was not combined with that of ethanol. The selective cannabinoid CB(1) receptor antagonist SR 141716A (N-(piperidin-1-yl)-5-(4-chlorophenyl)-1(2, 4-dichloro-phenyl)-4-methyl-1H-pyrazole carboxamide.HCl) at the dose of 1 mg/kg reversed the amnesic effect of THC, 10 mg/kg, suggesting that the effect is mediated by this receptor subtype. The synergism of ethanol and THC was not detected when an inter-trial interval of 1 min was adopted. The present findings are in keeping with the notion that Cannabis derivatives impair memory processes and provide evidence for a synergic action of THC and ethanol, thus emphasizing the risks consequent to their co-administration.     

Physical dependence following prolonged ethanol or t-butanol administration to rats

Rats were fed on liquid diets containing ethanol or t-butanol. On removal of either alcohol from the diet after 4–20 days, withdrawal reactions were observed. The range of withdrawal signs produced by the two alcohols were identical although the time course of the withdrawal reactions differed. Administration of one alcohol prevented the appearance of a withdrawal reaction in rats dependent on the other alcohol. Depletion of brain noradrenaline and dopamine did not prevent the development of physical dependence on either alcohol. Thus, neither aldehyde formation nor brain catecholamines appear to be involved in the development of physical dependence on these alcohols.     

Free-choice ethanol intake and ethanol metabolism in the hamster and rat

Hamsters, as previously reported, demonstrated greater ethanol intake and preference than rats. However, as ethanol was gradually added to a sweet solution, hamster ethanol intakes did not consistently exceed ethanol metabolic capacity for prolonged periods. In ethanol-naive hamsters and rats, alcohol dehydrogenase activities and ethanol metabolic rates of isolated hepatocytes in vitro and blood ethanol elimination rates in vivo show consistent large interspecific differences corresponding to the species' differences in ethanol intake and preference. The data suggest a limiting role of ethanol metabolism in the regulation of maximized free-selection ethanol intake by rodents, and provide an explanation for the absence of continuously elevated blood ethanol levels and alcohol withdrawal syndrome in hamsters during periods of comparatively high daily ethanol intake.     

Effect of cocaine on food intake in rats

In rats trained to eat during a five-hour daily period, cocaine (10, 15, and 25 mg/kg) depressed food intake. The anorexia was seen during the 1st h only, with no effect on total food intake.This work was taken in part from a thesis submitted by DCB in 1976, in partial fulfillment of the requirements for the degree of Master of Arts, Dep't of Psychology, SUNY —Binghamton