ABSTRACT
Ethanol drinking was assessed in the P/NP, HAD1/LAD1, and HAD2/LAD2 lines of rats under environmental conditions that produce schedule-induced polydipsia. Female rats (n = 8/line), maintained at 85% of free-feeding body weights, underwent daily 1-h sessions during which 45-mg food pellets were delivered every 60 s. Water, 2, 4, 8, 16, or 32% w/v ethanol solution was available from a single bottle for 8 consecutive sessions at each concentration, with blood-ethanol levels (BELs) determined after selected sessions. P and HAD2 rats drank more water and ethanol than their non-preferring counterparts, while HAD1 and LAD1 rats did not differ. Ethanol intake and BELs were positively correlated (r = 0.75) across lines. Finally, rats were allowed 14 daily choice sessions with 8% ethanol and water concurrently available. Water intake generally exceeded ethanol intake in all lines, while P rats drank similar amounts of both fluids. These line differences indicate pleiotropic effects of genes that mediate ethanol intake and schedule-induced behaviors.
Subject(s)
Alcohol Drinking/genetics , Ethanol/pharmacology , Thirst , Alcohols/pharmacology , Animals , Behavior, Animal , Body Weight , Choice Behavior/drug effects , Conditioning, Operant/drug effects , Drinking/drug effects , Drinking/genetics , Environment , Female , Rats , Rats, Wistar , Time FactorsABSTRACT
BACKGROUND: The behavioral effects of neuropeptide Y (NPY) attributed to its actions in the hypothalamus are complex and include effects on feeding, sedation, and the hypothalamic-pituitary-adrenal axis. NPY infused into the paraventricular nucleus (PVN) increases ethanol intake in unselected rats. High-alcohol-drinking (HAD1) and low-alcohol-drinking (LAD1) rats differ in basal NPY levels in the PVN, and HAD1, but not LAD1, rats exhibit decreases in ethanol intake after infusion of NPY into the ventricles. This study examined whether NPY infused into the PVN alters ethanol intake in HAD1 and LAD1 rats. METHODS: Female HAD1 (n = 14) and LAD1 (n = 18) rats were given 24-hr free-choice continuous access to 15% (v/v) ethanol and water for 6 weeks and then implanted bilaterally with cannulas aimed at the PVN. Two weeks later, rats received a series of microinfusions, each separated by 1 week, that included four doses of NPY (0.0, 0.25, 0.5, and 1.0 microg). Ethanol, water, and food were available ad libitum after infusions. All rats received a final microinfusion of 1.0 microg of NPY, after which ethanol and water, but no food, were made available for 2 hr. RESULTS: During the 2 hr after infusion, NPY yielded dose-dependent increases in both water and food consumption. With food concurrently available, the 0.25- and 1.0-microg doses of NPY did not alter baseline ethanol intake, whereas the 0.5-microg dose increased ethanol intake. Infusion of 1.0 microg of NPY in the absence of food yielded a decrease in water intake and an increase in ethanol intake relative to the same dose in the presence of food. Twenty-four hours after infusion, there were no effects of NPY on water and food intake, and increases in ethanol intake were no longer apparent. CONCLUSIONS: Increases in ethanol intake after infusion of NPY into the PVN may depend on NPY dose and whether food is concurrently available.
Subject(s)
Alcohol Drinking/genetics , Ethanol/administration & dosage , Neuropeptide Y/administration & dosage , Paraventricular Hypothalamic Nucleus/drug effects , Animals , Dose-Response Relationship, Drug , Eating/drug effects , Eating/physiology , Female , Paraventricular Hypothalamic Nucleus/physiology , RatsABSTRACT
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.
Subject(s)
Alcohol Drinking/drug therapy , Anxiety/drug therapy , Ethanol/administration & dosage , Neuropeptide Y/pharmacology , Sucrose/administration & dosage , Alcohol Drinking/genetics , Animals , Anxiety/genetics , Female , Humans , Maze Learning/drug effects , Maze Learning/physiology , Neuropeptide Y/therapeutic use , Rats , Species SpecificityABSTRACT
BACKGROUND: Neuropeptide Y (NPY) deficient mice consume more ethanol than controls, whereas NPY over-expressing mice consume less ethanol than controls. Thus, ethanol drinking may be inversely associated with NPY activity. To determine whether exogenously administered NPY would alter ethanol intake, two experiments were conducted. METHODS: A within-subject design was used with intracerebroventricular (ICV) administration of NPY or artificial cerebral spinal fluid (aCSF) into the lateral ventricles. Infusions were separated by 2 to 7 days. In experiment 1, male Wistar rats (n = 10) were tested for the effects of NPY on an intake of 5% sucrose or 8% (w/v) ethanol during daily 2-hr testing periods with food and water available at all other times. In experiment 2, male alcohol-preferring (P) and alcohol-nonpreferring (NP) rats (n = 8/line) were tested for the effects of NPY on 8% (w/v) ethanol intake. RESULTS: In experiment 1, NPY (5, 10, 20 microg) significantly increased sucrose intake relative to aCSF baseline in Wistar rats, a finding consistent with previous observations of the orexigenic effects of the peptide. However, NPY (10 microg) did not alter ethanol intake in Wistar rats. In experiment 2, NPY (5 and 10 microg) significantly decreased ethanol intake in P rats, but not in NP rats. CONCLUSION: The reduction in ethanol intake seen with the P rats is consistent with the postulated negative relationship between NPY activity and ethanol intake. The lack of effect of NPY on ethanol intake in Wistar and NP rats may be related to the lower baseline levels of ethanol intake in these rats or to differential central nervous system basal NPY activity or sensitivity to the peptide.
Subject(s)
Alcohol Drinking/drug therapy , Neuropeptide Y/administration & dosage , Alcohol Drinking/genetics , Animals , Injections, Intraventricular , Male , Rats , Rats, Wistar , Species SpecificityABSTRACT
Alcohol-preferring rats (Alko alcohol or AA) were tested for taste reactivity to water, sucrose, quinine, and a range of alcohol concentrations (5-40%) both before and after a period of continuous alcohol access. The alcohol-avoiding line of rats (Alko nonalcohol or ANA) was also tested for comparison. It was found that AA rats displayed greater ingestive reactivity to alcohol compared to ANA rats both before and after a three-week period of continuous access to 10% alcohol (during which time AA rats drank significantly more alcohol than ANA rats). AA rats also made significantly more ingestive responses to a 0.3 M sucrose solution and a 0.0005 M quinine solution. Differences between AA rats and ANA rats in aversive reactivity appeared only after the alcohol consumption tests; AA rats made significantly fewer aversive responses to the 30% and 40% concentrations after continuous alcohol access. AA rats also made significantly more aversive responses to the quinine solution. The results suggest that line differences between AA rats and ANA rats in the reactivity response to alcohol solutions have been selected in association with the original selection phenotype of alcohol consumption.
Subject(s)
Alcohol Drinking , Alcoholism/genetics , Central Nervous System Depressants/administration & dosage , Ethanol/administration & dosage , Taste/drug effects , Animals , Breeding , Female , Male , Muscle Relaxants, Central/administration & dosage , Quinine/administration & dosage , Rats , Sucrose/administration & dosageABSTRACT
OBJECTIVE: This study examined whether repeated daily treatment with naloxone prevents expression of a genetic predisposition toward high alcohol drinking in rats selectively bred for alcohol preference (P line). METHODS: In phase 1, alcohol-naive male rats were given food and water ad libitum and were pretreated with naloxone (2.5, 5.0, or 10.0 mg/kg, IP) or saline prior to scheduled access to alcohol (2 h/day) for 30 days. In phase 2, naloxone treatment was suspended for 30 days while rats continued to receive food and water ad libitum and scheduled access to alcohol. In phase 3, alcohol access was suspended for 14 days while rats continued to receive food and water ad libitum. In phase 4, daily pretreatment with naloxone or saline, followed by scheduled access to alcohol, was reinstated for an additional 30 days. RESULTS: Naloxone dose-dependently retarded acquisition of alcohol drinking. Following discontinuation of naloxone treatment, alcohol intake increased to levels comparable to those seen in the saline-treated group. Naloxone dose-dependently suppressed reinstatement of alcohol drinking (relapse) after a period of imposed abstinence. CONCLUSIONS: The results suggest that naloxone retards the acquisition of alcohol drinking and suppresses reinstatement of alcohol drinking in rats genetically predisposed toward high alcohol intake.
Subject(s)
Alcohol Drinking/drug therapy , Genetic Predisposition to Disease , Naloxone/therapeutic use , Alcohol Drinking/genetics , Analysis of Variance , Animals , Male , Narcotic Antagonists/therapeutic use , RatsABSTRACT
Rat lines selectively bred for high ethanol consumption consume more saccharin solution than do their low-ethanol-consuming counterparts. The present study utilized the technique of reciprocal selection to examine the reliability of the saccharin/ethanol relationship; specifically, consumption of 1-10% ethanol solution was measured in rats selectively bred for high vs. low saccharin consumption (Occidental HiS and LoS lines). HiS rats consumed more ethanol than did LoS rats. These results support the idea that individual differences in ethanol and saccharin consumption share some common mechanism(s).
Subject(s)
Ethanol/administration & dosage , Saccharin/administration & dosage , Animals , Body Weight , Breeding , Drinking , Female , Male , Phenotype , Rats , Sex Characteristics , SolutionsABSTRACT
The effect of blocking delta opioid receptors on alcohol aversion was examined in female alcohol-preferring (P) rats using a conditioned taste aversion (CTA) paradigm. In experiment 1, alcohol naive P rats were given i.p injections of 0.5, 1.0 or 1.5 g alcohol/kg BW or saline, paired with consumption of a banana-flavored solution during 5 conditioning trials. Alcohol in a dose of 0.5 g/kg was not aversive while the two higher doses (1.0 and 1.5 g/kg) were both aversive in the CTA paradigm. In experiment 2, the effect of the selective delta opioid receptor antagonist, naltrindole (NTI), on alcohol aversion was examined. Rats were pretreated with NTI in doses of 2.5, 5.0, 10.0 or 20.0 mg/kg before conditioning using the nonaversive dose of alcohol from Experiment 1. As in experiment 1, the 0.5 g/kg dose of alcohol did not produce a CTA. Administration of NTI alone in doses of 2.5, 5.0 or 10.0 mg/kg did not produce a CTA. However, when the nonaversive dose of alcohol (0.5 g/kg) was combined with NTI in a dose of either 5.0 or 10.0 mg/kg, an aversion to alcohol was seen. The highest dose of NTI (20 mg/kg) produced a CTA when given either alone and in combination with alcohol. The results indicate that blocking the action of opioid peptides at the delta opioid receptor can make a nonaversive dose of alcohol aversive which suggests that opioid peptides, acting via the delta opioid receptor, play an important role in regulating alcohol aversion.
Subject(s)
Alcohol Drinking/psychology , Endorphins/physiology , Enkephalins/physiology , Animals , Conditioning, Psychological , Dose-Response Relationship, Drug , Ethanol/blood , Female , Naltrexone/analogs & derivatives , Naltrexone/pharmacology , Rats , Rats, Wistar , Receptors, Opioid, delta/antagonists & inhibitorsABSTRACT
High, low, and control alcohol-sensitive (HAS, LAS, CAS, respectively) rats were tested for their perception of the taste of alcohol using the taste reactivity test. Reactivity tests with a single concentration of sucrose and quinine were also done. After initial taste reactivity, all rats were tested for alcohol consumption in a standard two-bottle test (water in the second bottle). Postconsumption taste reactivity tests completed the experiment. Results indicated that HAS, LAS, and CAS rats did not differ significantly in their taste reactivity response to a range of alcohol concentrations (5-40%), nor did they differ significantly in response to sucrose or quinine. Reactivity responses were similar for each group before and after the consumption tests. Despite the lack of line differences in taste reactivity, HAS and LAS rats consumed significantly less alcohol than the CAS rats during the two-bottle access tests. The present results are in contrast to research done with rats selectively bred for alcohol consumption (Alcohol Preferring and Nonpreferring rats, High Alcohol Drinking and Low Alcohol Drinking rats), which exhibit clear line differences in patterns of reactivity changes following alcohol access. The selection phenotype of alcohol sensitivity appears to be independent of rats' behavioral response to the taste of alcohol.
Subject(s)
Ethanol/pharmacology , Taste/drug effects , Alcohol Drinking , Animals , RatsABSTRACT
Confirmed high saccharin (HiS)-consuming and low saccharin (LoS)-consuming rats were compared in their taste response to saccharin using a continuous intraoral infusion procedure. On 2 separate days, rats were infused with 0.1% saccharin (rate = 1 ml/min) until they rejected fluid via passive drip or forceful fluid expulsion (at which time infusion was stopped for 30 s), and then again rejected fluid within 30 s after infusion was reinitiated. Two dependent measures were collected during infusion procedures: latency to first fluid rejection and total infusion time. On the first infusion day, HiS and LoS rats produced similar latencies to first rejection and total infusion times. However, HiS rats displayed significantly longer latencies to first rejection than LoS rats on the second infusion day. The results indicate that continuous infusion procedures exposed differences between HiS and LoS lines, but only after an initial experience with saccharin, albeit a relatively short exposure. The absence of immediate line differences with infusion procedures suggests that preference differences for saccharin between HiS and LoS lines are not mediated by brainstem taste reflexes, but rather are guided by associative processes accomplished above the brainstem.
Subject(s)
Food Preferences/physiology , Genotype , Saccharin/administration & dosage , Taste/genetics , Animals , Male , Motivation , Rats , Rats, Inbred Strains , Reaction Time/genetics , Selection, GeneticABSTRACT
Three experiments examined the effects of the training-to-testing interval on alcohol aversions. In Experiments 1 and 2, rats learned a taste aversion to a 4% (v/v) alcohol solution using lithium chloride as the illness agent. With a between-groups design, subjects were tested with 1%, 4%, or 7% alcohol, beginning either 2 or 21 days after training. In both experiments, results showed that rats learned aversions to the trained 4% alcohol that generalized to the nontrained 1% and 7% concentrations. Furthermore, in Experiment 1 aversions to 1% and 7% alcohol were stronger in groups tested 21 days after training relative to groups tested 2 days after training. When the strength of the illness agent was reduced in Experiment 2, aversions to all concentrations of alcohol were stronger at the delayed testing interval. Experiment 3 ruled out the possibility that enhanced alcohol avoidance at delayed testing was the result of spontaneous recovery of neophobia. The results suggest that taste aversions to alcohol become stronger with time. Possible mechanisms for this "incubation effect" are discussed. The present findings have implications for improving emetic therapy as a treatment for human alcoholics.