Intermittent exposure to a social stimulus enhances ethanol drinking in rats

The present experiment evaluates the effects of intermittent exposure to a social stimulus on ethanol and water drinking in rats. Four groups of rats were arranged in a 2x2 factorial design with 2 levels of Social procedure (Intermittent Social vs Continuous Social) and 2 levels of sipper Liquid (Ethanol vs Water). Intermittent Social groups received 35 trials per session. Each trial consisted of the insertion of the sipper tube for 10 s followed by lifting of the guillotine door for 15 s. The guillotine door separated the experimental rat from the conspecific rat in the wire mesh cage during the 60 s inter-trial interval. The Continuous Social groups received similar procedures except that the guillotine door was raised during the entire duration of the session. For the Ethanol groups, the concentrations of ethanol in the sipper [3, 4, 6, 8, 10, 12, 14, and 16% (vol/vol)] increased across sessions, while the Water groups received 0% ethanol (water) in the sipper throughout the experiment. Both Social procedures induced more intake of ethanol than water. The Intermittent Social procedure induced more ethanol intake at the two highest ethanol concentration blocks (10-12% and 14-16%) than the Continuous Social procedure, but this effect was not observed with water. Effects of social stimulation on ethanol drinking are discussed.     

Autoshaping induces ethanol drinking in nondeprived rats: evidence of long-term retention but no induction of ethanol preference

The effects of autoshaping procedures (paired vs. random) and sipper fluid (ethanol vs. water) on sipper-directed drinking were evaluated in male Long-Evans rats maintained with free access to food and water. For the paired/ethanol group (n=16), autoshaping procedures consisted of presenting the ethanol sipper (containing 0% to 28% unsweetened ethanol) conditioned stimulus (CS) followed by the response-independent presentation of food unconditioned stimulus (US). The random/ethanol group (n=8) received the sipper CS and food US randomly with respect to one another. The paired/water group (n=8) received only water in the sipper CS. The paired/ethanol group showed higher grams per kilogram ethanol intake than the random/ethanol group did at ethanol concentrations of 8% to 28%. The paired/ethanol group showed higher sipper CS-directed milliliter fluid consumption than the paired/water group did at ethanol concentrations of 1% to 6%, and 15%, 16%, 18%, and 20%. Following a 42-day retention interval, the paired/ethanol group showed superior retention of CS-directed drinking of 18% ethanol, relative to the random/ethanol group, and superior retention of CS-directed milliliter fluid drinking relative to the paired/water group. When tested for home cage ethanol preference using limited access two-bottle (28% ethanol vs. water) procedures, the paired/ethanol and random/ethanol groups did not differ on any drinking measures.     

Effects of removing food on maintenance of drinking initiated by pairings of sipper and food

Two experiments evaluated the effects of removing food presentations on the maintenance of drinking induced by experience with sipper — food pairings. In Exp 1, ethanol drinking was induced in non-deprived Long-Evans rats by Pavlovian conditioning procedures employing an ethanol sipper as conditioned stimulus (CS) and food pellet as unconditioned stimulus (US). The Paired/Ethanol group received presentations of the ethanol sipper CS followed immediately by the response-independent presentation of the food pellet US. The Random/Ethanol group received the ethanol sipper CS and food US randomly with respect to one another. For both groups, the concentration of ethanol in the sipper CS [(3%, 4%, 6%, 8% (vol./vol.)] was increased across sessions, and, as in previous studies employing low concentrations of ethanol in non-deprived rats (i.e., maintained with free access to food in their home cages), the two procedures induced comparable levels of sipper CS-directed ethanol drinking. Removing food US presentations had no effect on sipper CS-directed ethanol drinking in either group. In Exp 2, groups of non-deprived Long-Evans rats were trained either with water or ethanol in the sipper CS paired with food US. Removing food US presentations had no effect on ethanol drinking in the Paired/Ethanol group, but water drinking in the Paired/Water group declined systematically across sessions. Results indicate that food US presentations contribute to the maintenance of water drinking but not to the maintenance of ethanol drinking. Implications for accounts of ethanol drinking based on Pavlovian sign-tracking, behavioral economics and intermittent sipper procedures are considered.     

Ethanol exposure as inducer of stable voluntary ethanol drinking in the male rat

The effects of restricted 'Saturday night drinking' on voluntary ethanol intake was tested in male rats. During a treatment period of 57 weeks the animals (group B) could choose between ethanol and water for 24 h each week. After this period of choice they received ethanol (2.0 g/kg) i.v. Total weekly exposure was around 6-7 g/kg. Of two control groups, one was given i.p. injections of saline once a week (group A) and the other, in addition to saline injections, a continuous choice between ethanol (10%) and water as drinking fluid (group C). Weekly ethanol exposure was approximately 14 g/kg in group C. During a testing period of 46 weeks group A and C had continuous access to a choice between ethanol and water. After week 5 of the testing period concentrations of ethanol varied in 3-week intervals. For each tested concentration (5, 15, 20 and 25%) intake was calculated as g/kg per day based on the total period. For the reference concentration (10%) corresponding intake was calculated on 2 weeks prior to and 2 weeks after the tested concentration. In group B there was always a very strong correlation (r = 0.86-0.99) between intake of the different tested concentration and the corresponding reference concentration. This indicates that a strong individual preference for a defined daily dose of ethanol had developed in these rats. The corresponding relation was less developed in group C especially when higher concentrations of ethanol were tested. At the end of the testing period voluntary ethanol intake was slightly higher in group B and C when compared to group A. Analyses of blood ethanol levels at defined times during the testing period indicated an interrupted ethanol intake with occasionally substantial blood levels. Thus intermittent ethanol exposure can induce a voluntary ethanol drinking pattern in male rats which might be used as an animal model of alcoholism.     

Daily patterns of ethanol drinking in adolescent and adult, male and female, high alcohol drinking (HAD) replicate lines of rats

The rationale for our study was to determine the pattern of ethanol drinking by the high alcohol-drinking (HAD) replicate lines of rats during adolescence and adulthood in both male and female rats. Rats were given 30 days of 24 h free-choice access to ethanol (15%, v/v) and water, with ad lib access to food, starting at the beginning of adolescence (PND 30) or adulthood (PND 90). Water and alcohol drinking patterns were monitored 22 h/day with a “lickometer” set-up. The results indicated that adolescent HAD-1 and HAD-2 males consumed the greatest levels of ethanol and had the most well defined ethanol licking binges among the age and sex groups with increasing levels of ethanol consumption throughout adolescence. In addition, following the first week of adolescence, male and female HAD-1 and HAD-2 rats differed in both ethanol consumption levels and ethanol licking behavior. Adult HAD-1 male and female rats did not differ from one another and their ethanol intake or licking behaviors did not change significantly over weeks. Adult HAD-2 male rats maintained a relatively constant level of ethanol consumption across weeks, whereas adult HAD-2 female rats increased ethanol consumption levels over weeks, peaking during the third week when they consumed more than their adult male counterparts. The results indicate that the HAD rat lines could be used as an effective animal model to examine the development of ethanol consumption and binge drinking in adolescent male and female rats providing information on the long-range consequences of adolescent alcohol drinking.     

Sexual orientation in male rats prenatally exposed to ethanol

Previous studies have shown that prenatal ethanol exposure causes feminization of the male offspring, as evidenced by display of female sexual response (lordosis), when mounted by a stud male. In the present study we examined whether or not the feminization induced by prenatal ethanol exposure also affected a different aspect of sexually motivated behavior, namely, the approach towards a receptive female normally displayed by male rats. The testing apparatus consisted of an open-field arena with two small boxes in which were placed the stimulus animals, in one box a male rat, in the other a receptive female. The partition between the stimulus and the experimental animals consisted of a metal net allowing both animals to see and smell each other without actual physical contact. The tendency to approach the receptive female or the male was assessed by the proportion of the observation period the experimental male spent near the receptive female or the male rat, respectively. The experiment was performed on the adult male offspring of mothers consuming a liquid diet containing 5% ethanol, giving rise to a daily ethanol intake of about 14 g/kg. One group of control mothers was given a liquid diet without alcohol but isocaloric with the alcohol-containing diet. Another control group had free access to water and lab chow. The results showed that male offspring of both control groups devoted 29% of the observation period near the receptive female as compared to 13% near the male. The ethanol-exposed males on the other hand devoted as much time, 20%, to the male as to the receptive female.(ABSTRACT TRUNCATED AT 250 WORDS)     

Alteration of voluntary ethanol and saccharin consumption by the neurosteroid allopregnanolone in mice

RATIONALE: The neurosteroid 3 alpha-hydroxy-5 alpha-pregnan-20-one (allopregnanolone, ALLOP) is a positive modulator of gamma-aminobutyric acid type A (GABA(A)) receptors. Recent findings indicate that ethanol (EtOH) and ALLOP share common mechanisms of action and that ALLOP may modulate some of EtOH's abuse-related effects. OBJECTIVES: The present studies investigated whether ALLOP pretreatment altered voluntary EtOH consumption in male and female C57BL/6J mice, and voluntary saccharin and quinine consumption in male C57BL/6J mice. METHODS: Mice had access to two drinking tubes containing water versus 5% or 10% (v/v) EtOH or a tastant for 2 h each day at the beginning of the dark cycle. Following establishment of stable consumption, animals received 2 days of vehicle followed by 3 days of ALLOP injections (0, 3.2, 10, or 17 mg/kg, IP), immediately prior to EtOH or tastant access. RESULTS: Prior to injection, the 2-h baseline dose of the 10% EtOH solution consumed was 1.31 g/kg (expt 1) or 2.46 g/kg (expt 3) for male and 2.21 g/kg (expt 2) for female mice. Baseline intake of the 5% EtOH solution was 0.60 g/kg for males and 0.75 g/kg for females (expt 5). In males, ALLOP administration significantly and dose-dependently increased consumption of both EtOH solutions during the first hour of availability without affecting water intake. In females, ALLOP did not significantly alter EtOH consumption. Lastly, ALLOP significantly increased saccharin, but not quinine, consumption in males (females were not tested). CONCLUSIONS: ALLOP may increase voluntary EtOH consumption in male mice by altering its reinforcing effects. The lack of significant effect on quinine and water consumption suggests that ALLOP does not simply increase consumption of all fluids.     

Chronic ethanol tolerance through free-choice drinking in the P line of alcohol-preferring rats

The objective of this study was to determine if the selectively bred P line of alcohol-preferring rats would develop behavioral (neuronal) tolerance with free-choice drinking of ethanol. Adult, male P rats were divided into four groups. One group (FCE) received food, water and a 10% (v/v) ethanol solution ad lib, while the control group (C) had only food and water. The other two groups received either a liquid diet containing 5% (v/v) ethanol (LDE) or a control liquid diet (LDC). All groups were kept on their respective feeding regimens for 14 days. The mean (+/- SEM) ethanol intakes for the FCE and LDE groups were 6.8 +/- 0.5 and 9.9 +/- 0.4 g ethanol/kg body wt./day, respectively. A shock-motivated jumping task was used to test for tolerance. Each rat received an IP injection of 2.5 g ethanol/kg and was tested every 15 minutes for recovery to a criterion of 75% of the performance level achieved with training. All rats were tested twice, once on the day before beginning their feeding regimens (day 0) and again 14 days later. Tolerance was assessed from differences in time of recovery to criterion performance and in blood alcohol concentrations (BACs) at recovery on day 0 vs. day 14. The mean recovery times for the C, FCE, LDC, and LDE groups on day 0 were 177 +/- 6, 170 +/- 6, 143 +/- 10 and 153 +/- 13 minutes, respectively, and the BACs were 219 +/- 6, 222 +/- 5, 220 +/- 19 and 214 +/- 6 mg%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Chronic ethanol tolerance as a result of free-choice drinking in alcohol-preferring rats of the WHP line

The development of tolerance to alcohol with chronic consumption is an important criterion for an animal model of alcoholism and may be an important component of the genetic predisposition to alcoholism. The aim of this study was to determine whether the selectively bred Warsaw High Preferring (WHP) line of alcohol-preferring rats would develop behavioral and metabolic tolerance during the free-choice drinking of ethanol. Chronic tolerance to ethanol-induced sedation was tested. The loss of righting reflex (LRR) paradigm was used to record sleep duration in WHP rats. Ethanol (EtOH)-naive WHP rats received a single intraperitoneal (i.p.) injection of 5.0 g ethanol/kg body weight (b.w.), and sleep duration was measured. Subsequently, rats had access to a 10% ethanol solution under a free-choice condition with water and food for 12 weeks. After 12 weeks of the free-choice intake of ethanol, the rats received another single i.p. injection of 5.0 g ethanol/kg b.w., and sleep duration was reassessed. The blood alcohol content (BAC) for each rat was determined after an i.p. injection of 5 g/kg of ethanol in naive rats and again after chronic alcohol drinking at the time of recovery of the righting reflex (RR). The results showed that the mean ethanol intake was 9.14 g/kg/24 h, and both sleep duration and BAC were decreased after chronic ethanol intake. In conclusion, WHP rats exposed to alcohol by free-choice drinking across 12 weeks exhibited increased alcohol elimination rates. Studies have demonstrated that WHP rats after chronic free-choice drinking (12 weeks) of alcohol develop metabolic tolerance. Behavioral tolerance to ethanol was demonstrated by reduced sleep duration, but this decrease in sleep duration was not significant.     

Daily patterns of ethanol drinking in peri-adolescent and adult alcohol-preferring (P) rats

Alcohol abuse among adolescents continues to be a major health problem for our society. Our laboratory has used the peri-adolescent alcohol-preferring, P, rat as an animal model of adolescent alcohol abuse. Even though peri-adolescent P rats consume more alcohol (g/kg/day) than their adult counterparts, it is uncertain whether their drinking is sufficiently aggregated to result in measurable blood ethanol concentrations (BECs). The objectives of this study were to examine daily alcohol drinking patterns of adolescent and adult, male and female P rats, and to determine whether alcohol drinking episodes were sufficiently aggregated to result in meaningful BECs. Male and female P rats were given 30 days of 24 h free-choice access to alcohol (15%, v/v) and water, with ad lib access to food, starting at the beginning of adolescence (PND 30) or adulthood (PND 90). Water and alcohol drinking patterns were monitored 22 h/day with a "lickometer" set-up. The results indicated that (a) peri-adolescent P rats consumed more water and total fluids than adult P rats, (b) female P rats consumed more water and total fluids than male P rats, (c) there were differences in alcohol, and water, licking patterns between peri-adolescent and adult and female and male P rats, (d) individual licking patterns revealed that alcohol was consumed in bouts often exceeding the amount required to self-administer 1 g/kg of alcohol, and (e) BECs at the end of the dark cycle, on the 30th day of alcohol access, averaged 50 mg%, with alcohol intakes during the last 1 to 2 h averaging 1.2 g/kg. Overall, these findings indicate that alcohol drinking patterns differ across the age and sex of P rats. This suggests that the effectiveness of treatments for reducing excessive alcohol intake may vary depending upon the age and/or sex of the subjects being tested.     

Influence of age at drinking onset on the alcohol deprivation effect and stress-induced drinking in female rats

We have recently observed increased stress responsiveness with regard to alcohol consumption in male rats that consumed alcohol since their adolescent period. Thus, early age at drinking onset can induce enhanced stress-induced alcohol drinking in male rats. However, it is not known whether female rats respond in a similar way. Therefore, we compared the drinking behavior of two female Wistar rat groups--one that acquired alcohol consumption during adolescence (adolescent group) and the other that acquired their drinking during adulthood (adult group) in a model of long-term voluntary alcohol drinking with repeated deprivation and stress phases. Furthermore, we studied the influence of age at drinking onset on the efficacy of acamprosate treatment. Thirty-nine female Wistar rats aged 31 days (adolescents) and 71 days (adults) were given ad libitum access to water, as well as to 5% and 20% ethanol solutions during an observation period of 29 weeks. A deprivation phase of 14 days was introduced following 8 weeks of access to alcohol in order to measure the alcohol deprivation effect (ADE). After 15 and 25 weeks of alcohol access, all animals were subjected for 3 consecutive days of forced swim and electric foot-shock stress, respectively. After 29 weeks of access to alcohol all animals underwent a second deprivation phase and the subsequent ADE was measured either under acamprosate (200 mg/kg) or vehicle treatment. Drinking before the first deprivation phase was not different between animal groups. However, the expression of the first ADE was more pronounced in adult female rats and alcohol intake stayed increased for the remainder of the experiment in the adult group. Both repeated swim stress and foot-shock stress produced a more pronounced increase in ethanol consumption in the adolescent group compared to the adult group. Acamprosate reduced relapse-like drinking in the adult female rat group. However, it had no effect on the ADE in the adolescent group. In conclusion, female rats that initiate alcohol consumption during adolescence might be more susceptible to stress-induced alcohol consumption. Adolescent alcohol drinking might also result in a reduced response to acamprosate.     

Dopamine D3 receptor knockout mice and the motivational effects of ethanol

Dopamine D3 receptors have been implicated in the behavioral effects of abused drugs including ethanol. The present experiments characterized the acquisition of ethanol-induced place conditioning and ethanol self-administration in D3 knockout (D3 KO) mice compared with C57BL/6J (C57) mice. For place conditioning, D3 KO and C57 mice received six pairings of a tactile stimulus with ethanol (3 g/kg i.p.). D3 KO mice showed higher basal locomotor activity levels in comparison with the C57 mice during conditioning. Ethanol produced similar magnitudes of conditioned place preference in both genotypes. In a two-bottle drinking procedure, mice of each genotype received 24 h access to water and either 3% or 10% v/v ethanol. No difference was noted between D3 KO and C57 mice in either consumption or preference. In an operant self-administration procedure using 23 h sessions, D3 KO and C57 mice received access to 10% v/v ethanol on an FR4 schedule of reinforcement, food on an FR1 schedule of reinforcement and water from a sipper tube. D3 KO and C57 mice had similar response rates of ethanol and food as well as similar water intakes. Overall, these results indicate that elimination of D3 receptor function has little influence on ethanol reward or intake.     

Characteristics of ethanol drinking patterns under schedule-induced polydipsia

Rats were induced to consume concentrations of ethanol between 5% and 10% (w/v) using the schedule-induced polydipsia technique. Although the substitution of ethanol solutions for water disrupted the usual post-pellet pattern of drinking, large amounts of ethanol were consumed and sound-induced convulsions were observed during ethanol withdrawal. In subsequent experiments, other rats chose 5% and sometimes 10% ethanol solutions over water where both water and ethanol were freely available during the first session of exposure to ethanol. Convulsions and wild running behavior could be observed in some of these rats after only 8 days of drinking, even though ethanol was freely available at all times. Use of the schedule-induced polydipsia technique served to bring the rats into early contact with the ethanol, but rats that received the same number of food pellets in a dish rather than by the schedule drank almost as much ethanol as did the rats receiving ethanol by the schedule. Rats with free access to food pellets drank very little ethanol.     

Social rank and social separation as determinants of alcohol drinking in squirrel monkeys

Rationale  Alcohol may be self-administered for its anxiolytic effects to alleviate symptoms of stress, but different types of stressors have varying effects on alcohol intake. Social stress is particularly relevant to alcohol drinking, and a primate model of stress-induced alcohol self-administration would be useful. Objective  The objective of the study is to determine if social stresses of different lengths and intensities affect voluntary alcohol intake in monkeys. Materials and methods  Subjects were adult male and female squirrel monkeys (Saimiri sciureus) housed in social colonies. Subjects were trained to drink a solution of ethanol and sucrose, alternated daily with a control solution of quinine and an equal concentration of sucrose in 15-min sessions. Drinking was tested during 20-min acute, social separations and 1-week, extended, social separations. Dominance status was quantified using observational records of social interactions within the colonies. Salivary cortisol was sampled in the home colony and during extended social separation. Results  Dominance rank was inversely correlated with alcohol intake during social housing but was not correlated with control fluid intake. Acute social separation abolished drinking of both fluids, accompanied by increased anxiety-like behavior. Extended social separation increased salivary cortisol and alcohol drinking but not control fluid intake in males. In females, drinking was unchanged by extended separation. Conclusions  The chronic stress of social subordination is correlated with increased alcohol drinking. Acute social separation stress suppresses drinking behavior, while extended separation preferentially increases alcohol intake in a subset of individuals. These findings suggest that social stressors of different time-courses and intensities have opposing effects on alcohol self-administration.     

Sex differences in L-type calcium current after chronic ethanol consumption in rats

Chronic ethanol consumption elicits a progressive cardiac contractile dysfunction, and studies in rats suggest that this alcoholic heart muscle disease is more pronounced in males than females. Cellular changes associated with the ethanol-induced cardiotoxicity remain largely undefined; however, it is possible that L-type Ca(2+) channel current (I(Ca,L)) is affected. Using whole-cell patch-clamp techniques, this study examined I(Ca,L) in adult ventricular myocytes isolated from male and female P-rats that had consumed drinking water (controls) or a 25% ethanol/water mixture for 14 months. The peak amplitude and maximum conductance of I(Ca,L) were 32 and 26% greater, respectively, in cardiomyocytes isolated from ethanol-consuming compared to control male rats. In contrast, no differences in the amplitude or conductance of I(Ca,L) were observed when comparing myocytes isolated from control and ethanol-consuming females. Ethanol treatment had no significant effects on the kinetics I(Ca,L) inactivation or on steady-state activation and inactivation in either gender. In conclusion, male but not female cardiomyocytes respond to chronic ethanol consumption with an increased I(Ca,L) that may represent a compensatory response to the depressed contractility.     

Increase in free choice oral ethanol self-administration in catechol-o-methyltransferase gene-disrupted male mice

The effect of catechol-O-methyltransferase (Comt) gene disruption on the voluntary oral consumption of water, ethanol (2.5-20%, v/v) and cocaine (0.1-0.8 mg/ml) was studied in the free-choice, two-bottle paradigm in male and female mice. Solutions containing ethanol or cocaine, or tap water were available ad libitum from drinking burettes for 4 weeks. Catechol-O-methyltransferase-deficient male mice consumed significantly more ethanol than their wild-type male littermates. In contrast, female mice did not show genotype differences in the consumption of ethanol solutions. During the cocaine experiment, male mice developed either a side preference or an aversion that obscured cocaine consumption. This pattern of drinking was not dependent on Comt genotype. In female mice, Comt genotype was not associated with cocaine consumption. In conclusion, disruption of Comt gene influenced ethanol consumption in a gender-dependent manner in mice, supporting the hypothesis that low catechol-O-methyltransferase activity is one of the predisposing factors for high alcohol consumption in males.     

Effects of chronic ethanol consumption on aortic constriction in male and female rats

This study was designed to determine if gender influences the effects of chronic ethanol intake on vasoconstrictive responsiveness. Ethanol-preferring rats were allowed ad libitum access to tap water or tap water containing 20% or 30% ethanol for 16 weeks. All of the ethanol groups consumed more daily calories than their respective controls, and female rats consumed more ethanol calories per unit body mass than their male counterparts. Following treatment, endothelium-intact and endothelium-denuded thoracic aortic rings were used to examine the contractile response to phenylephrine. Ethanol consumption did not alter vasoconstriction in endothelium-intact aortae from either gender. In contrast, males, but not females, demonstrated an ethanol-associated increase in the maximum response to phenylephrine in endothelium-denuded preparations. Aortae from male rats that consumed 20% and 30% ethanol showed an increased contractility of 37% and 85%, respectively. These data indicate that gender influences the vasoconstrictive effects elicited by chronic ethanol consumption and suggest that males may be more susceptible to the associated hypertension.     

Modeling binge-like ethanol drinking by peri-adolescent and adult P rats

Alcohol binge-drinking, especially among adolescents and young adults, is a serious public health concern. The present study examined ethanol binge-like drinking by peri-adolescent [postnatal days (PNDs 30-72)] and adult (PNDs 90-132) alcohol-preferring (P) rats with a drinking-in-the-dark-multiple-scheduled-access (DID-MSA) procedure used by our laboratory. Male and female P rats were provided concurrent access to 15% and 30% ethanol for three 1-h sessions across the dark cycle 5 days/week. For the 1st week, adolescent and adult female P rats consumed 3.4 and 1.6 g/kg of ethanol, respectively, during the 1st hour of access, whereas for male rats the values were 3.5 and 1.1 g/kg of ethanol, respectively. Adult intakes increased to ~ 2.0 g/kg/h and adolescent intakes decreased to ~ 2.5 g/kg/h across the 6 weeks of ethanol access. The daily ethanol intake of adult DID-MSA rats approximated or modestly exceeded that seen in continuous access (CA) rats or the selection criterion for P rats (≥ 5 g/kg/day). However, in general, the daily ethanol intake of DID-MSA peri-adolescent rats significantly exceeded that of their CA counterparts. BELs were assessed at 15-min intervals across the 3rd hour of access during the 4th week. Ethanol intake was 1.7 g/kg vs. 2.7 g/kg and BELs were 57 mg% vs. 100 mg% at 15- and 60-min, respectively. Intoxication induced by DID-MSA in female P rats was assessed during the 1st vs. 4th week of ethanol access. Level of impairment did not differ between the 2 weeks (106 vs. 97 s latency to fall, 120 s criterion) and was significant (vs. naïve controls) only during the 4th week. Overall, these findings support the use of the DID-MSA procedure in rats, and underscore the presence of age- and sex-dependent effects mediating ethanol binge-like drinking in P rats.     

Differences in the consumption of ethanol and flavored solutions in three strains of rats

Several studies have shown a correlation between ethanol consumption and the intake of flavored solutions in rats, particularly sweet solutions. This observation, however, has not been shown in all strains of rats. The present study examined whether the intake of ethanol and that of flavored solutions would be related in Lewis (LEW), Wistar (WIS), and Wistar Kyoto (WKY) rats. During phase I, all rats were presented with water and a flavored solution following a continuous access paradigm as developed by Overstreet et al.: quinine (0.25% wt/vol), saccharin (0.1% wt/vol), ethanol (ETOH) (10% vol/vol), and saccharin-quinine (SQ) solutions (0.4% wt/vol-0.04% wt/vol). During phase II, fluid presentations were reduced to a 10-min limited access schedule and were presented in the same order. Results showed strain differences in intake and preference for ETOH and SQ during both phases, but not in quinine or saccharin intake. ETOH and saccharin intake were only correlated in the LEW strain during limited access drinking, while ETOH and SQ intake were correlated in the LEW strain as well as when all strains were collapsed during continuous drinking. These findings suggested that any association between ETOH and sweet intake may not be generalizable to all rat strains. The animals used in this study may have differed in taste sensitivity, as low ETOH-consuming LEW rats were sensitive to the bitter taste of quinine alone, as well as when mixed with saccharin. Sensitivity to bitter tastes may be an important predictor of low ETOH consumption and/or preference. These data provide further evidence for the role of taste factors in the mediation of voluntary ETOH consumption in rats.     

Acquisition of oral phencyclidine self-administration in rhesus monkeys: effect of sex

Rationale: There are increasing reports of sex differences in the etiology of drug abuse in humans. A nonhuman primate model is useful for examining sex as a variable in drug abuse. Objectives: To determine whether there are sex differences in the acquisition of oral phencyclidine (PCP) self-administration and to compare the effect of altered feeding conditions on drug self-administration in male and female monkeys. Methods: Acquisition of orally delivered PCP was studied using 7 female and 11 male adult rhesus monkeys. Initially, the monkeys were not food restricted, and they were given access to water under concurrent fixed-ratio (FR) 1 schedules during daily 3-h sessions. Each lip-contact response on a drinking spout resulted in a 0.3 ml liquid delivery. After baseline levels of water intake were obtained for 5 days, water was replaced with PCP (0.125 mg/ml) at both drinking spouts. Body weights were then reduced to 85% of free-feeding weights, and the monkeys were fed 30 min before the session began. The FR value was increased from 1 to 2, 4, and 8, at both drinking spouts. As a final step in the procedure, water and PCP were concurrently available at the two spouts under FR 8 schedules. Acquisition of PCP-reinforced behavior was considered to have occurred if PCP intake was consistently greater than water intake. Results: Lip-contact responses and liquid deliveries were not significantly different between the females and males throughout the acquisition period, but there was a significant increase in responding and decrease in liquid intake as FR increased, and a significant increase in PCP consumption due to food restriction that did not differ in males and females. On a milligram per kilogram basis, female monkeys consumed nearly twice as much PCP as the males; however, this effect was not significant. The females showed significantly higher PCP than water intake while the males consumed approximately equal amounts of PCP and water. Of the seven females, 100% met the acquisition criterion of significantly greater PCP than water intake, while only 36.4% of the males met the criterion. Conclusion: These results concur with previous rat studies and indicate that female monkeys are more likely than males to acquire drug-reinforced behavior. Received: 4 October 1999 / Final version: 20 January 2000