Acquisition Of Ethanol Intake Research Articles

Behavioral Consequences of Repeated Nicotine During Adolescence in Alcohol‐Preferring AA and Alcohol‐Avoiding ANA Rats

Epidemiological studies suggest that exposure to nicotine at adolescent age is associated with increased potential to use alcohol and that genetic predisposition may further increase the risk. The present study addressed adolescent vulnerability to repeated nicotine exposure and its influence on subsequent ethanol self-administration by investigating interactions between nicotine-induced behavioral sensitization and voluntary ethanol consumption in alcohol preferring AA (Alko Alcohol) and alcohol nonpreferring ANA (Alko Non-Alcohol) rat lines selected for differential ethanol intake. Adolescent and adult rats received 10 injections of nicotine (0.5 mg/kg s.c.), given every second day from postnatal day (Pnd) 27 and 75, respectively. Nicotine-induced (0.5 mg/kg) locomotor activity was measured acutely after the first injection, and after the repeated treatment with nicotine on Pnds 52 and 86 in the adolescent groups and on Pnd 99 in the adult groups. After this, acquisition of voluntary ethanol (10% v/v) consumption as well as nicotine-induced (0.5 mg/kg) ethanol intake was measured in the AA rats. Adolescent AA rats were more sensitive than adolescent ANA rats to the locomotor effects of nicotine. They were also stimulated more than adult AA rats, but such a difference was not found among ANA rats. Adolescent and adult rats did not differ in their susceptibility to nicotine-induced behavioral sensitization. Genetic predisposition to ethanol self-administration did not interact with development of behavioral sensitization in either adolescents or adults. Acquisition of ethanol intake was enhanced in the adolescent groups relative to the adult groups in a manner that was independent of the nicotine treatment. An increase in ethanol intake was found after challenging animals with nicotine, and this effect was enhanced in the nicotine-treated adolescent group. These findings provide no or little support for the views that adolescent animals are more sensitive to the neurobehavioral effects of repeated exposure to nicotine and that exposure to nicotine in adolescence may contribute to enhanced vulnerability to ethanol abuse. Furthermore, genetic predisposition to high or low ethanol self-administration does not seem to be a factor that influences individual vulnerability to the neurobehavioral effects of repeated administration of nicotine.

Inhibition of 5α‐Reduced Steroid Biosynthesis Impedes Acquisition of Ethanol Drinking in Male C57BL/6J Mice

Allopregnanolone (ALLO) is a physiologically relevant neurosteroid modulator of GABA(A) receptors, and it exhibits a psychopharmacological profile that closely resembles the post-ingestive effects of ethanol. The 5alpha-reductase inhibitor finasteride (FIN), which inhibits biosynthesis of ALLO and structurally related neurosteroids, was previously demonstrated to reduce the maintenance of limited-access ethanol consumption. The primary aim of the current work was to determine whether FIN would reduce the acquisition of drinking in ethanol-naïve mice. Male C57BL/6J (B6) mice were acclimated to a reverse light/dark schedule, and were provided ad libitum access to chow and water. Following habituation to vehicle injections (VEH; 20% w/v beta-cyclodextrin; i.p.) administered 22-hour prior to drinking sessions with water only, mice were divided into 3 treatment groups: vehicle control (VEH), 50 mg/kg FIN (FIN-50), and 100 mg/kg FIN (FIN-100). Twenty-two hours after the first treatment, mice were permitted the inaugural 2-hour limited access to a 10% v/v ethanol solution (10E) and water. The acquisition of 10E consumption and underlying drinking patterns were assessed during FIN treatment (7 days) and subsequent FIN withdrawal (13 days) phases. FIN dose-dependently blocked the acquisition of 10E drinking and prevented the development of ethanol preference, thereby suggesting that the GABAergic neurosteroids may be important in the establishment of stable drinking patterns. FIN-elicited reductions in 10E intake were primarily attributable to selective and marked reductions in bout frequency, as no changes were observed in bout size, duration, or lick rates following FIN treatment. FIN-treated mice continued to exhibit attenuated ethanol consumption after 2 weeks post-treatment, despite a full recovery in brain ALLO levels. A second study confirmed the rightward and downward shift in the acquisition of ethanol intake following 7 daily FIN injections. While there were no significant group differences in brain ALLO levels following the seventh day of ethanol drinking, ALLO levels were decreased by 28% in the FIN-50 group. Although the exact mechanism is unclear, FIN and other pharmacological interventions that modulate the GABAergic system may prove useful in curbing ethanol intake acquisition in at-risk individuals.

Effects of ethanol on locomotor and anxiety-like behaviors and the acquisition of ethanol intake in Lewis and spontaneously hypertensive rats

The purpose of the present study was to investigate whether Lewis (LEW) and spontaneously hypertensive rats (SHR), characterized in numerous behavioral tests as strains with high-anxiety and low-anxiety, respectively, could differ in their sensitivity to the effects of ethanol in the elevated plus maze (EPM) and the open field (OF), two classical models of anxiety/emotionality, as well as in the acquisition of ethanol drinking behavior. It was also of interest to examine the relationship between sweet and bitter fluids preference and ethanol intake. SHR and LEW rats were given saline or ethanol injections (0.6 or 1.2 g/kg, ip.) and tested in the EPM and OF. Subsequently the same animals were given continuous free choice between water and ethanol solution (2–8%). Additional groups of animals were exposed to a free-choice regimen between saccharin (0.002–0.09%) or quinine (0.0001–0.0015%) and water. The low dose of ethanol (0.6 g/kg) induced anxiolytic-like effects and intensive locomotor activation mainly in SHR rats tested in the OF arena. Overall, LEW counterparts were unaffected in OF test. In oral self-administration paradigm, SHR rats consumed significantly more ethanol than LEW rats. Concerning other solutions, SHR rats consumed large amounts of saccharin compared with LEW rats. These data indicate that the SHR preference for ethanol intake may be positively related to their differential sensitivity to the anxiolytic/stimulant effects of ethanol and to the sensitivity of this strain for saccharin reinforcement. In addition, these findings provide evidence that the SHR strain may represent a useful genetic and pharmacological tool to investigate ethanol drinking traits.

Maternal separation has no effect on voluntary ethanol intake in female Wistar rats

Adverse experiences, early in life or during adulthood, can increase the vulnerability for development of drug dependence. Investigators have shown that short and prolonged periods of maternal separation during the postnatal period can affect voluntary ethanol intake in male rats. Recent study findings have indicated sex-dependent effects of maternal separation, and, in the current study, the effects of maternal separation on acquisition of voluntary ethanol intake in female Wistar rats were investigated. Rat pups were subjected to daily maternal separation for 15 min (MS15) or 360 min (MS360) during the first 3 weeks of life or reared under normal animal facility rearing (AFR) conditions. During 25 days, starting at 10 weeks of age, the effects of maternal separation on acquisition of voluntary ethanol intake were investigated. In contrast with previous study results for male rats, neither MS15 nor MS360 affected acquisition of voluntary ethanol intake in female rats. A stressful situation in adulthood, restraint stress, resulted in a significant increase in ethanol intake during the restraint period compared with baseline levels in the animals reared under normal AFR conditions, an effect that persisted throughout the postrestraint period. In rats subjected to MS15 or MS360, a significant increase in ethanol intake was shown during the postrestraint period compared with baseline levels. The current study findings therefore give further evidence for sex differences in the consequences of maternal separation. Compared with previous findings in male rats, acquisition of ethanol intake was not affected, and restraint-induced effects were less pronounced but more prolonged, in female rats.

Maternal separation has no effect on voluntary ethanol intake in female Wistar rats

Adverse experiences, early in life or during adulthood, can increase the vulnerability for development of drug dependence. Investigators have shown that short and prolonged periods of maternal separation during the postnatal period can affect voluntary ethanol intake in male rats. Recent study findings have indicated sex-dependent effects of maternal separation, and, in the current study, the effects of maternal separation on acquisition of voluntary ethanol intake in female Wistar rats were investigated. Rat pups were subjected to daily maternal separation for 15 min (MS15) or 360 min (MS360) during the first 3 weeks of life or reared under normal animal facility rearing (AFR) conditions. During 25 days, starting at 10 weeks of age, the effects of maternal separation on acquisition of voluntary ethanol intake were investigated. In contrast with previous study results for male rats, neither MS15 nor MS360 affected acquisition of voluntary ethanol intake in female rats. A stressful situation in adulthood, restraint stress, resulted in a significant increase in ethanol intake during the restraint period compared with baseline levels in the animals reared under normal AFR conditions, an effect that persisted throughout the postrestraint period. In rats subjected to MS15 or MS360, a significant increase in ethanol intake was shown during the postrestraint period compared with baseline levels. The current study findings therefore give further evidence for sex differences in the consequences of maternal separation. Compared with previous findings in male rats, acquisition of ethanol intake was not affected, and restraint-induced effects were less pronounced but more prolonged, in female rats.

Maternal Separation Alters Acquisition of Ethanol Intake in Male Ethanol-Preferring AA Rats

Maternal Separation Alters Acquisition of Ethanol Intake in Male Ethanol-Preferring AA Rats

Naltrexone Suppresses Ethanol Intake in 6‐Hydroxydopamine–Treated Rats

The suppressive effect of opioid antagonists, such as naltrexone, on ethanol intake has been suggested to be based on the interference with ethanol-induced stimulation of dopamine release in the nucleus accumbens. The aim of this study was to determine whether reduction of dopamine innervation to the nucleus accumbens with the neurotoxin 6-hydroxydopamine (6-OHDA) alters naltrexone-induced suppression of ethanol consumption. Because the mesolimbic dopaminergic neurons have also been implicated in ethanol reinforcement, the effects of 6-OHDA on the maintenance and acquisition of ethanol intake were also studied. To damage accumbal terminals of the mesolimbic dopamine neurons, alcohol-preferring Alko Alcohol (AA) rats were given bilateral injections of 6-OHDA or vehicle into the nucleus accumbens after pretreatment with desipramine and pargyline. The effect of the lesion on the acquisition or maintenance of ethanol self-administration was studied in animals having continual access to ethanol solution (10% v/v) and water. Subsequently the effect of naltrexone on ethanol consumption was determined. Naltrexone (0.03-3.0 mg/kg subcutaneously) suppressed ethanol consumption in a dose-dependent manner both in 6-OHDA-treated and control animals given a daily 90-min access to ethanol solution. When the rats had continual access to ethanol, there was a clear day-to-day decline in ethanol intake during the first 5 days of the 7-day naltrexone treatment (10 mg/kg subcutaneously). 6-OHDA treatment had no effect on either the acquisition or maintenance of ethanol self-administration. Postmortem analysis of the brain dopamine content revealed approximately 92% depletion of dopamine in the nucleus accumbens of the 6-OHDA-treated rats. The suppressive effect of naltrexone does not depend on naltrexone's interaction with dopaminergic terminals in the nucleus accumbens. Furthermore, the role of the mesolimbic dopamine pathway is probably not central either in the acquisition or maintenance of ethanol self-administration in alcohol-preferring AA rats.

Caffeine promotes ethanol drinking in rats: Examination using a limited-access free choice paradigm

There is growing evidence that caffeine may alter the pattern of intake of a variety of drugs. The present study was designed to assess the effect of caffeine pretreatment on voluntary ethanol consumption. The first experiment examined the effect of caffeine on the acquisition of ethanol intake in a limited-access-choice procedure in which water and ethanol were presented concurrently. Male Wistar rats, exposed to food and water ad lib, were presented with a daily 1-h choice session between water and progressively increasing concentrations of ethanol (2–10%). Each ethanol concentration was made available for 4–6 days for a total of 20 days of access to ethanol. Intraperitoneal injections of caffeine (5 or 10 mg/kg) or saline were administered to the rats 30 min prior to each choice session. Caffeine produced a dose-related facilitation in ethanol drinking whereby the lower caffeine dose produced enhancement in ethanol drinking. The second experiment examined the effect of caffeine on the maintenance of established ethanol consumption. Male Wistar rats, initially acclimatized to increasing concentrations of ethanol (2%–10), were presented with an additional 18 ethanol (10%) presentations, comprised of a 6-day baseline period followed by 6 days of treatment where animals were given one of three doses of caffeine (2.5, 5 or 10 mg/kg) or saline prior to ethanol presentation. A final 6-day post-treatment period followed treatment. These results revealed an inverted-U effect of caffeine dose on ethanol ingestion where the low and high caffeine doses produced no effect but the moderate dose of 5 mg/kg enhanced ethanol drinking that persisted throughout the post-treatment period. A third experiment revealed that caffeine did not alter levels of blood ethanol within the time period used for the ethanol drinking session.