Appetitive and Consummatory Behaviors in the Control of Ethanol Consumption: A Measure of Ethanol Seeking Behavior

Models of ethanol self-administration in animals have demonstrated that ethanol can reinforce a variety of behaviors, independent of ethanol's caloric or fluid properties. However, the processes that control self-administration remain unclear. Determining factors related to ethanol seeking behavior, independent of consumption, Is central to the concepts of intake regulation. The model described in this article proposes a method to separate the initial appetitive (seeking) behavior from the following consummatory (drinking) behavior to assess each behavior type. Rats were trained to lever press to gain access to a drinking tube connected to a fluid bottle containing either 10Y0 ethanol or 3% sucrose for 20 min. When the response requirement to obtain access to the tube was increased, it was found that both solutions supported the same amount of responding (breakpoint was at approximately a fixed ratio 32 requirement), indicating equal reinforcer strength. However, regardless of the response requirement, if access to the fluids occurred, intakes were not changed. This suggests that factors besides those of reinforcer efficacy are important in controlling the size of the consummatory bout. Based on these findings, we believe that this model will be useful in determining factors related to seeking behaviors and the control of drinking bout size.     

Effects of Raclopride in the Nucleus Accumbens on Ethanol Seeking and Consumption

BACKGROUND: Nucleus accumbens dopamine has been shown to play a role in the processing of behaviorally relevant stimuli and to mediate ethanol-reinforced responding. Previous research that used a fixed-ratio schedule of responding maintained by the presentation of small dippers (0.1 ml) of ethanol demonstrated that the dopamine D2 antagonist, raclopride, decreased total responding for ethanol by both delaying the onset of responding and causing the early termination of lever-press behavior. Because these studies required animals to continuously respond to obtain access to small amounts of ethanol over a period of self-administration, this procedure assessed a combination of appetitive (seeking) and consummatory (drinking) behavior. The paradigm used in the present study separated the appetitive or seeking response from the consummatory response to assess the effects of raclopride on both types of ethanol-related behaviors. METHODS: Male Long-Evans rats were trained to emit a fixed number of lever-press responses that resulted in access to a drinking tube that contained 10% ethanol for 20 min, once each day. We measured the effects of microinjections of raclopride (1.0, 3.0, and 10.0 microg/subject) into the nucleus accumbens, before the sessions, on appetitive and consummatory responding. RESULTS: Raclopride delayed the onset of ethanol-seeking (appetitive responding) at all doses and decreased the number of responses made at the low and high doses. The rate of responding, however, was unaffected. Raclopride had no effect on the latency to begin consuming ethanol or on any of the characteristics of the initial bout of ethanol intake at all doses tested. Total ethanol intake was decreased, after an initially "normal" pattern of self-administration, following only the highest dose of raclopride. Mean ethanol intake (g/kg) was 0.54 (+/-0.03) after no injection, 0.51 (+/-0.04) after sham treatment, and 0.38 (+/-0.05) after 10 microg of raclopride. CONCLUSIONS: The procedural separation of the seeking and intake responses used in this experiment allowed us to assess the effects of dopamine receptor antagonism in the nucleus accumbens on these two different behaviors. Overall, appetitive responding that preceded the delivery of an ethanol solution was more sensitive to raclopride treatment than was consummatory responding. These findings are consistent with a stimulus-processing function of the mesolimbic dopamine system.     

Increased consumption but not operant self-administration of ethanol in mice lacking the RIIbeta subunit of protein kinase A

BACKGROUND: Accumulating evidence indicates that adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) is involved in the neurobiological responses to ethanol. Previous reports indicate that mice lacking the RIIbeta subunit of PKA (RIIbeta(-/-)) voluntarily consume more ethanol than wild-type controls (RIIbeta(+/+)) using 2-bottle testing procedures. Although such procedures primarily measure consummatory behavior, operant self-administration procedures allow analysis of consummatory as well as appetitive or "ethanol-seeking" behavior (i.e., lever pressing is required to gain access to the ethanol solution). Therefore, we determined whether the high ethanol consumption characteristic of RIIbeta(-/-) mice would be complemented by increased appetitive ethanol-seeking behavior in an operant paradigm. METHODS: RIIbeta(-/-) (n=8) and RIIbeta(+/+) (n=8) mice were initially sucrose-faded until they were lever responding for nonsweetened ethanol (10, 14, and 18%). Following the self-administration testing, RIIbeta(+/+) and RIIbeta(-/-) mice were given access to 2 bottles, one containing water and the other ethanol to replicate the voluntary ethanol drinking data previously from our laboratory. Finally, immediately after voluntary consumption all mice were again tested for self-administration of 10% ethanol. Alterations in the reinforcement schedule were also explored as RIIbeta(+/+) and RIIbeta(-/-) mice were tested for self-administration of 10% ethanol at FR-3 and FR-5 schedules. RESULTS: The RIIbeta(-/-) mice displayed lower operant responding for ethanol and food reinforcement compared with RIIbeta(+/+) controls. However, this effect was driven by a significant increase in lever responses made by female RIIbeta(+/+) mice. When the excessive lever responses of the female RIIbeta(+/+) mice are accounted for, the RIIbeta(-/-) mice show ethanol lever responses comparable to controls. Following operant self-administration testing, RIIbeta(-/-) mice of both sexes consumed more ethanol solution compared with RIIbeta(+/+) mice during 2-bottle testing. CONCLUSIONS: Increased ingestion of ethanol by RIIbeta(-/-) mice is likely the result of altered PKA activity within neuronal pathways that control ethanol-consummatory behaviors. Conversely, the RIIbeta subunit of PKA appears not to play a critical role in neuronal pathways that regulate appetitive behaviors directed at obtaining ethanol. Finally, increased operant self-administration of food and ethanol by female wild-type mice was absent in female RIIbeta(-/-) mice, suggesting that normal PKA signaling may be part of a general, and sex-dependent, mechanism involved with reinforcement-seeking behavior.     

Ethanol and sucrose seeking and consumption following repeated administration of the GABA(B) agonist baclofen in rats

BACKGROUND: Baclofen, a GABA(B) agonist, has been found to decrease alcohol craving in humans and to nonselectively decrease ethanol intake in some rodent models. This experiment assessed the effects of repeated administration of baclofen on reinforcer seeking and consumption using the sipper tube appetitive/consummatory model of ethanol access. METHODS: Subjects were divided into 2 groups and trained to make 30 lever press responses that resulted in access to either 10% ethanol or 2% sucrose in a sipper tube-drinking spout for 20 minutes. Three doses of baclofen were tested (0.3, 1.0, and 3.0 mg/kg) and each drug treatment was assessed using the following schedule: Monday, saline; Tuesday to Thursday, baclofen; and Friday, saline. RESULTS: The low dose of baclofen had no effect on the seeking or intake of either sucrose or ethanol, and the 1.0 mg/kg dose also had no effect on the appetitive, seeking response. However, the 1.0 mg/kg dose significantly decreased sucrose intake (from an average of 0.56 to 0.41 g/kg) and significantly increased ethanol intake (from an average of 0.77 to 1.00 g/kg). Similarly, the high dose (3.0 mg/kg) decreased sucrose intake and had a tendency to increase ethanol intake while decreasing both sucrose seeking and ethanol seeking. CONCLUSIONS: Overall, baclofen treatment affected reinforcer intake at doses that had no effect on reinforcer seeking, and effective doses decreased both sucrose seeking and ethanol seeking. Moreover, the effects on reinforcer intake were disparate, in that baclofen increased ethanol drinking and decreased sucrose drinking. The nonspecific effects of baclofen suggest that the GABA(B) system may be involved in general consummatory or drinking behaviors and does not appear to specifically regulate ethanol-motivated responding.     

Breakpoint Determination and Ethanol Self-Administration Using an Across-Session Progressive Ratio Procedure in the Rat

BACKGROUND: Progressive ratio schedules are used to determine the "breakpoint" or limit to the amount of "work" that a subject is willing to perform to obtain a reinforcer. Reinforcing efficacy is inferred from the breakpoint values, which are typically measured in a single session by increasing the number of responses required for successive reinforcer presentations. This procedure is not feasible, however, when assessing the reinforcing efficacy of a substance that can change as a function of its physiological actions during self-administration, as in the case of ethanol. METHODS: The present study made use of a procedure that increased the response requirement across single daily sessions rather than within a session. Completion of the response requirement in each daily session resulted in the presentation of a drinking tube that allowed for self-administration of ethanol for a 20-min period. This procedure made possible the assessment of ethanol-directed appetitive (number of lever presses) and consummatory (number of licks and intake volume) behaviors. Reliable responding for 10% ethanol was initiated using sucrose-substitution on a fixed ratio (FR) 4 schedule in male Long Evans rats. Then four successive breakpoint determinations were made which were separated by a return to the FR4 schedule to re-establish baseline responding. RESULTS: The results indicated that there was an increase in breakpoint values from the first to the second determination, which was then stable over the following three determinations. Individual rats reached breakpoints as high as 240 lever presses to receive access to 10% ethanol and maintained ethanol intake over sessions in the 1.0 g/kg range. Ethanol intake (g/kg), however, was stable across all four determinations (mean 0.86 +/- 0.06 to 1.01 +/- 0.10). Moreover, ethanol intake was not related to the preceding appetitive responding, as no differences between intake on the session before a breakpoint (high FR) and the following baseline period (FR4) were observed. CONCLUSIONS: This model provides an assessment of the distinct mechanisms that mediate ethanol-seeking versus ethanol consumption in subjects that drink measurable amounts of ethanol, with the appetitive behaviors not altered by the pharmacological effects of ethanol.     

Reinstatement of ethanol-seeking behavior following intravenous self-administration in Wistar rats

BACKGROUND: In animal models of alcoholism, subjects are traditionally trained to self-administer ethanol via the oral route. However, ethanol is also self-administered intravenously (IV), a paradigm which offers several advantages over oral self-administration methods, including immediate delivery to the bloodstream, more rapid onset of pharmacological effects, and elimination of the need to utilize tastants or sweeteners to mask the aversive orosensory properties of ethanol. However, no studies to date have examined reinstatement of ethanol-seeking behavior in animals with a history of IV ethanol self-administration. METHODS: Male Wistar rats were implanted with indwelling jugular vein catheters and trained to self-administer ethanol IV (1% v/v solution, equivalent to 1 mg/kg) in an operant lever-pressing paradigm in twice daily 1 hour sessions. Each IV delivery of ethanol was paired with presentation of a light-tone complex stimulus. After stabilization of response patterns, IV self-administration behavior was subjected to extinction procedures. Next, animals were exposed to the three types of stimuli known to reinstate ethanol-seeking behavior: presentation of ethanol-associated cues, a priming dose of ethanol (0.5 g/kg i.p.), or exposure to stress via administration of the anxiogenic compound yohimbine (2.5 mg/kg i.p.) or its corresponding vehicle. RESULTS: During the maintenance phase of self-administration, animals exhibited significantly more presses on the lever that delivered the ethanol solution than the inactive lever, indicating that IV ethanol functioned as a positive reinforcer. Following extinction, it was found that ethanol-seeking behavior could be reinstated by all three types of stimuli (cues, ethanol priming, and yohimbine). Vehicle injection did not affect responding on either lever. CONCLUSIONS: Ethanol serves as a reinforcer when self-administered IV, and following extinction, ethanol-seeking behavior can be reinstated by ethanol-associated cues, ethanol priming, or a pharmacological stressor. Thus, reinstatement of ethanol-seeking behavior in animals with a history of IV ethanol self-administration may be a novel animal model of relapse.     

Effect of naloxone on appetitive and consummatory phases of ethanol self-administration

BACKGROUND: The opioid system has been implicated in ethanol self-administration. Morphine, an opiate agonist, can sometimes increase the amount of ethanol consumed, and opiate antagonists such as naloxone and naltrexone decrease the amount of ethanol consumed in both animals and humans. The objective of this study was to examine the effect of naloxone on appetitive (or seeking) and consummatory behaviors by using an operant model developed to separate these two phases of self-administration. METHODS: Intraperitoneal injections of naloxone (0.3-10 mg/kg) or vehicle were given before operant self-administration sessions to assess the effect on lever pressing (appetitive behavior) and subsequent consumption. Effects were measured in two groups of rats: one self-administered a 3% sucrose solution and the other a 10% ethanol solution. RESULTS: Naloxone dose-dependently decreased ethanol and sucrose consumption by an earlier cessation of drinking in the session compared with vehicle injection days. There were some effects on appetitive responding after treatment with naloxone, but none was statistically significant. CONCLUSIONS: Naloxone may decrease ethanol self-administration by decreasing the postingestive or pharmacological effects of alcohol. This model provides a new method for examining the effects of potential pharmacotherapeutics on alcohol self-administration behavior.     

Effect of ethanol self-administration on mu- and delta-opioid receptor-mediated G-protein activity

BACKGROUND: This study examined the effects of ethanol self-administration on mu- and delta-opioid receptor-mediated G-protein activity in specific brain regions of male Long Evans rats. METHODS: Rats were trained to self-administer ethanol by using a home-cage modification of the sucrose substitution paradigm. After 30 to 40 days of sucrose or sucrose/15% ethanol self-administration (20 min sessions, Monday-Friday), rats were killed for autoradiographic assays. Coronal sections of brains from sucrose and ethanol self-administering rats were collected and processed for basal and mu- and delta-stimulated [35S]guanosine-5'-O-(gamma-thio)-triphosphate (GTPgammaS) binding. Sections were exposed to film and then analyzed by using computer-assisted densitometry to determine levels of basal and agonist-stimulated [35S]GTPgammaS binding. RESULTS: Mu-opioid-stimulated [35S]GTPgammaS binding was decreased in the prefrontal cortex of brains from ethanol compared with sucrose self-administering rats. Mu-opioid-stimulated [35S]GTPgammaS binding was unchanged in the cingulate cortex, caudate-putamen, nucleus accumbens, amygdala, hypothalamus, thalamus, and locus ceruleus of ethanol compared with sucrose self-administering rats. Basal and delta-opioid-stimulated [35S]GTPgammaS binding did not differ between the two groups in the prefrontal cortex or any other region analyzed. CONCLUSIONS: These data demonstrate decreased mu-opioid-mediated G-protein activity in the prefrontal cortex of ethanol self-administering rats and suggest an interaction between ethanol and mu-opioid receptors in this region.     

Effects of acamprosate on neuronal receptors and ion channels expressed in Xenopus oocytes

Background: Acamprosate (calcium acetylhomotaurinate) has proven to be a moderately effective pharmacological adjunct for the treatment of alcoholism. However, the central nervous system mechanism by which acamprosate reduces alcohol relapse remains unclear. Here we survey a number of metabotropic receptors, ligand‐gated ion channels, and voltage‐gated ion channels, to determine if acamprosate has actions at these sites in the central nervous system. Methods: Xenopus oocytes were injected with cDNAs or cRNAs encoding metabotropic glutamate receptors 1 and 5, M1 muscarinic receptors, glycine α1 homomeric and α1β1 heteromeric receptors, γ‐aminobutyric acid A (GABA_Aα4β3δ, α4β3γ2s, and α1β2γ2s) receptors, vanilloid receptor 1, and various combinations of α and β subunits of voltage‐gated Na⁺ channels. Electrophysiological responses were measured using two‐electrode voltage clamp parameters after activation with agonists or voltage steps (for the voltage‐gated channels). Acamprosate (0.1 to 100 μM) was pre‐applied for 1 minute, followed by co‐application with agonist. Acamprosate was also applied with ethanol to determine if it altered ethanol responses at some of these receptors and channels. Results: None of the receptors or ion channels responded to acamprosate alone. Acamprosate also failed to alter the activation of receptors or channels by agonists or after activation of voltage‐gated channels. There was no effect of acamprosate on ethanol responses at GABA_Aα1β2γ2s receptors or Na⁺ channels. Conclusions: Acamprosate does not significantly modulate the function of these receptors and ion channels at clinically relevant concentrations. Thus, the clinical effectiveness of acamprosate in the treatment of alcoholism is not likely due to direct effects on these receptors or ion channels.     

Effects of naltrexone on alcohol self-administration in heavy drinkers

The mechanisms underlying the suppressant effects of naltrexone (NTX) on ad libitum alcohol drinking in a bar/restaurant setting were investigated in heavy beer drinkers. Fifty-one male and female heavy drinkers (mean age = 22) received 50 mg of NTX or placebo (PBO), p.o., on two separate occasions in a randomized, double-blind crossover protocol. After 7 days of taking medication, subjects were provided with the opportunity to consume beer ad libitum during two, 90-min test sessions that were held 1 to 2 weeks apart. Blood samples were collected on test days to ensure medication compliance and to measure blood levels of NTX and the active beta-naltrexol. Less beer was consumed during NTX treatment. NTX decreased urges to consume alcohol. NTX-treated subjects also took significantly longer to finish each glass of beer and were more likely to terminate beer drinking early. Self-report stimulation and ratings of positive mood states were lower during NTX treatment. Negative side effects of NTX, such as nausea and headache, were reported more frequently with NTX. Not all of the subjects decreased their beer intake on NTX, and some subjects drank more beer. Nonresponders to NTX were not related to blood levels of the active metabolite beta-naltrexol or to a family history of alcoholism. Overall, the results of this study suggest that NTX affects a number of the components of alcohol drinking sequence, including lowering cravings, decreasing the positive reinforcing effects of alcohol, and increasing headache and nausea, each of which may contribute to reducing alcohol intake.     

Effects of acamprosate on excitatory amino acids during multiple ethanol withdrawal periods

Background: Our previous studies on the effects of acamprosate on enhanced locomotion during repeated withdrawals are now extended to the effects of acamprosate on excitatory amino acids in the hippocampus during repeated ethanol withdrawals. Methods: In this study, Wistar rats were made ethanol dependent by 4 weeks of vapor inhalation. After this first cycle of chronic ethanol treatment, rats underwent repeated and alternate cycles of 24 hr withdrawals and 1 week of chronic ethanol treatment. The microdialysis technique was used together with high‐performance liquid chromatography and electrochemical detection to quantify different amino acids such as aspartate and glutamate. Results: An intraperitoneal administration of acamprosate (400 mg/kg) to naïve rats did not alter aspartate or glutamate levels compared with the saline groups. During the first cycle of ethanol withdrawal, the administration of acamprosate (400 mg/kg, intraperitoneally) 2 hr after the commencement of ethanol withdrawal decreased both aspartate and glutamate microdialysate levels when compared with their respective saline group. Acamprosate administration also significantly decreased glutamate levels during the third withdrawal compared with the saline group, whereas no changes were seen in aspartate levels. Conclusion: The results of this work demonstrate that acamprosate reduced the excitatory amino acid glutamate increase observed during repeated ethanol withdrawal. These effects of acamprosate may provide a protective mechanism against neurotoxicity by reducing excitatory amino acids, particularly glutamate.     

Effects of SR141716A on ethanol and sucrose self-administration

BACKGROUND: Previous studies have demonstrated that administration of central cannabinoid receptor (CB1) ligands can produce marked effects on ingestive behaviors. However, the possible relationship to ethanol self-administration has not been fully examined. The present series of experiments was designed to characterize further the role of CB1 receptors in appetitive and consummatory behaviors related to sucrose and ethanol. METHODS: To determine the relative contribution of CB1 receptors to ethanol seeking and consumption, a series of experiments was designed using the sipper-tube model. In this paradigm, the appetitive and consummatory phases of ethanol and sucrose self-administration are separated. In the appetitive phase, animals are required to complete a response requirement (16 lever presses) within 20 min. If the requirement is successfully completed, access to a sipper tube containing either sucrose or ethanol (consummatory phase) is made available for 20 min. RESULTS: In the ethanol condition, the CB1 receptor antagonist SR141716A (0.3-3.0 mg/kg, ip) produced dose-related decreases in the probability of response requirement completion without significantly affecting latency to first lever press or overall lever press rate. In the sucrose condition, SR141716A (0.3-3.0 mg/kg, ip) increased first lever press latency without affecting lever press rate. In the consummatory phase, SR141716A (0.3-3.0 mg/kg, ip) administration markedly decreased total intake and the total number of licks for both ethanol and sucrose. CONCLUSIONS: These data indicate that CB1 receptors are involved in mediating both appetitive and consummatory aspects of ingestive behaviors related to sucrose and ethanol.     

Effects of acamprosate on sleep during alcohol withdrawal: A double-blind placebo-controlled polysomnographic study in alcohol-dependent subjects

BACKGROUND: Sleep disturbances are frequently encountered in alcohol-dependent patients. Drugs improving sleep during abstinence from alcohol may play an important role in the recovery process. METHODS: In the present study, the effects of acamprosate, a drug successfully used in maintaining abstinence following alcohol withdrawal, were assessed by polysomnographic recordings. A parallel double-blind placebo-controlled study was conducted in 24 male DSM-IV alcohol-dependent subjects aged 35.9+/-1.2 years. Treatments (2 tablets of 333 mg acamprosate vs placebo t.i.d.) were initiated 8 days before alcohol withdrawal and continued during the 15 days following alcohol withdrawal. Polysomnographic assessments were recorded during acute withdrawal (the first 2 nights following withdrawal) and during postwithdrawal abstinence (the last 2 nights of the trial). RESULTS: Results show that, compared with placebo, acamprosate decreased wake time after sleep onset and increased stage 3 and REM sleep latency (all treatment effects with a p < 0.05 significance). Withdrawal effects themselves were also demonstrated as sleep efficiency (p < 0.01) and total sleep time (p < 0.05) were lower in abstinence nights versus withdrawal nights, whereas no significant treatment x withdrawal effect could be evidenced. Acamprosate was well tolerated during the entire course of the study. CONCLUSIONS: The present study shows that acamprosate ameliorates both sleep continuity and sleep architecture parameters classically described as disturbed in alcohol-dependent patients. From a clinical perspective, it suggests that an 8-day acamprosate prewithdrawal treatment is well tolerated and can attenuate the sleep disturbances engendered by alcohol withdrawal in alcohol-dependent subjects.     

Baseline trajectories of drinking moderate acamprosate and naltrexone effects in the COMBINE study

Background: The COMBINE study evaluated the effects of acamprosate, naltrexone, and the Combined Behavioral Intervention (CBI). In secondary analyses, our goals were to identify trajectories of any drinking prior to randomization, to characterize subjects in these trajectories, and to assess whether prerandomization trajectories predict drinking outcomes and moderate treatment response. Methods: We analyzed daily indicators of any drinking in 90 days prior to randomization using a trajectory‐based approach. General linear models and generalized logistic regression assessed main and interactive effects of prerandomization drinking trajectories and treatment on summary drinking measures during active treatment. Results: We identified five trajectories of any drinking prior to randomization: “T1: frequent drinkers”, “T2: very frequent drinkers”, “T3: nearly daily drinkers”, “T4: consistent daily drinkers”, and “T5: daily drinkers stopping early”. During treatment, “T3: nearly daily drinkers” and “T4: consistent daily drinkers” had significantly worse drinking outcomes than “T1: frequent drinkers”, while “T5: daily drinkers stopping early” had comparable drinking outcomes to “T1: frequent drinkers”. Acamprosate significantly increased the chance of abstinence from heavy drinking for the “T2: very frequent drinking” trajectory but decreased the chance of abstinence from heavy drinking for “T5: daily drinkers stopping early”. Naltrexone differentially improved rates of continuous abstinence for very frequent drinkers. Conclusions: Acamprosate benefited very frequent drinkers and contrary to expectations was associated with poorer response compared to placebo for consistent daily drinkers who had longer durations of pretreatment abstinence (e.g., ≥14 days). Baseline drinking trajectories also moderated naltrexone effects. These findings may help clinicians identify patients for whom acamprosate and naltrexone may be most beneficial.     

Effects of neuropeptide Y on sucrose and ethanol intake and on anxiety-like behavior in high alcohol drinking (HAD) and low alcohol drinking (LAD) rats

BACKGROUND: In a previous study, neuropeptide Y (NPY) administered into the lateral ventricles decreased ethanol intake in alcohol-preferring (P) rats but not in alcohol-nonpreferring (NP) or unselected Wistar rats. The purpose of the present investigation is to extend these findings in selectively-bred high-alcohol-drinking (HAD)1 and low-alcohol-drinking (LAD)1 rats by examining the effects of intracerebroventricularly administered NPY on the elevated plus maze test of anxiety and on ethanol and sucrose intake. METHODS: Female HAD1 and LAD1 rats were surgically implanted with cannula into the lateral ventricle. Following recovery, a test of anxiety was conducted in which the rats (n = 12-13/group) received either artificial cerebrospinal fluid (aCSF) or NPY (10 microg) 10 min prior to a 5-min test on an elevated plus maze. Following anxiety testing, 11 HAD and 11 LAD rats were trained to self-administer ethanol (8% w/v), and 5 HAD and 8 LAD rats were trained to self-administer sucrose (2.5%) during daily 2-hr sessions. A within-subject design was used in which the rats were pretreated once a week with aCSF, 5 microg NPY, or 10 microg NPY prior to the drinking sessions. RESULTS: HAD and LAD rats treated with aCSF did not differ in time spent in open arms of the plus maze. NPY increased time spent on the open arms to similar degrees in both rat lines. HAD rats consumed more ethanol and sucrose than LAD rats. NPY increased sucrose intake in both rat lines. However, the same doses of NPY reduced ethanol intake in HAD but not in LAD rats. CONCLUSION: The plus maze results indicated that selective breeding for high and low alcohol preference in the HAD1 and LAD1 rats, respectively, did not yield differences in anxiety-like behavior and in response to the anxiolytic effects of NPY. The increases in sucrose intake were consistent with the known orexigenic effects of NPY. The decreased ethanol intake following NPY administration in HAD rats was similar to previous observations with P rats and is consistent with the hypothesis that ethanol intake and NPY activity may be inversely related.     

Operant Self-Administration of Sweetened Versus Unsweetened Ethanol: Effects on Blood Alcohol Levels

BACKGROUND: Sweeteners are often added to ethanol solutions to increase ethanol intake. However, literature on studies that use human subjects and laboratory animals suggests that sucrose, other sugars, and carbohydrate-rich foods alter ethanol absorption and metabolism, which leads to lower blood alcohol levels (BAL) relative to ethanol absorbed alone. This experiment was designed to test whether the addition of the nutritive sweetener sucrose, or the nonnutritive sweetener saccharin, to a 10% ethanol solution, self-administered in an oral operant paradigm, affected BAL in rats relative to self-administration of an unsweetened 10% ethanol solution. METHODS: All rats were trained to lever press for ethanol by use of a saccharin fading procedure. Half of the rats then received 30-min sessions in which ethanol + 2% sucrose and water were available and were alternated daily with sessions in which ethanol + 0.2% saccharin and water were available. The other half of the rats went on to receive daily sessions of unsweetened ethanol and water. BAL were taken after these standard daily sessions as well as after a 1-week period of alcohol deprivation (to enhance ethanol intake). RESULTS: Rats responded for more ethanol + sucrose than unsweetened ethanol, but had lower BAL per gram ethanol consumed in both the baseline test and alcohol deprivation effect test. No effect of saccharin on BAL was detected. An additional experiment that examined the effects of four concentrations of both sucrose and saccharin on self-administration of ethanol and BAL showed that, whereas rats consumed more ethanol + sucrose than ethanol + saccharin, BAL were significantly lower per gram ethanol consumed in the sucrose group. CONCLUSIONS: These results confirm previous reports and suggest that the addition of sucrose to an ethanol solution can result in lower BAL relative to unsweetened ethanol in an oral operant self-administration paradigm.