Flavor preferences conditioned by intragastric ethanol with limited access training

In a prior study, ad libitum fed rats learned a strong preference (90%) for a flavored saccharin solution (conditioned stimulus, CS+) paired with concurrent intragastric (IG) infusions of 5% ethanol over another flavor (CS-) paired with water infusions in unlimited access sessions (22 h/day). The present study expanded the investigation of ethanol-conditioned preferences to limited access sessions (30 min/day). Experiment 1 revealed that ad lib or food-restricted rats failed to develop a CS+ preference using the same CS solutions (0.05% Kool-Aid+0.2% saccharin) and IG infusions that were effective with long-term training. Experiments 2 and 3 mimicked the parameters from a report of successful ethanol conditioning in deprived rats: ethanol (0.5 g/kg) or water was infused intragastrically 5 min before access to sweetened CS solutions flavored with HCl or NaCl. Rats learned to prefer the ethanol-paired CS+ when the flavors were mixed with 5% sucrose but not when mixed with 0.2% saccharin. Experiment 4 revealed that 5% sucrose solutions flavored with 0.25% Kool Aid also supported flavor preference conditioning by IG ethanol (0.5 g/kg). CS+ preferences were obtained in rats trained with ethanol infused 5 min before or concurrent with CS+ intake, but not in rats trained with ethanol infused 30 min before CS+ intake. These data confirm that flavor preferences can be conditioned by IG ethanol using a limited access procedure. However, in contrast to 22 h/day training, 30 min/day training requires more intense CS flavors and a nutritive sweetener. The preference reinforcing actions of ethanol may develop slowly and are thus most effective with long training sessions or when intense CS flavors are used in short training sessions.     

Naltrexone fails to block the acquisition or expression of a flavor preference conditioned by intragastric carbohydrate infusions

The effects of naltrexone on the expression and acquisition of flavor preferences conditioned by the postingestive actions of carbohydrates were investigated. Food-restricted rats (Experiment 1) were given one-bottle training with one flavored saccharin solution (CS+) paired with intragastric (IG) infusions of 16% sucrose, and another flavored saccharin solution (CS-) paired with water infusions. In two-bottle tests CS+ was preferred to CS-, and naltrexone (1.0-5.0 mg/kg) reduced total intake but not CS+ preference. In Experiment 2 food-restricted rats that received naltrexone (0.1 or 1.0 mg/kg; NTX group) throughout one-bottle training consumed less CS+ and CS- than did saline-treated control rats. Yet, the NTX and control groups displayed similar CS+ preferences during two-bottle tests when treated with saline or naltrexone (0.1-5.0 mg/kg). In Experiment 3, rats were trained to accept more CS+ than CS- in one-bottle tests. Naltrexone (0.1-2.5 mg/kg) reduced the one-bottle intakes of both solutions, and the rats continued to consume more CS+ than CS-. We conclude that the opioid system modulates the consumption of flavored solutions, but is not critically involved in the acquisition or expression of flavor preferences conditioned by IG carbohydrate.     

Flavor quality and ethanol concentration affect ethanol-conditioned flavor preferences

A previous report showed that outbred rats acquired preferences for a sweetened conditioned stimulus (CS) flavor paired with intragastric ethanol. To evaluate the role of sweet taste in ethanol conditioning, this study compared training with sweetened and unsweetened flavors. In Experiment 1, nondeprived rats were trained to drink one flavored solution (CS+, e.g., grape) paired with intragastric infusion of 5% ethanol and another (CS-, e.g., cherry) paired with intragastric water on alternate days. The volume of ethanol solution infused was matched to the volume of flavored solution the rats consumed. The sweet group's flavors initially contained 0.2% saccharin, reduced to 0.1%, 0.05%, and 0% over days; the plain group's flavors were unsweetened. The sweet group drank more and self-infused more ethanol during training and its preference for the CS+ over the CS- (without saccharin) exceeded that of the plain group (75% versus 62%). Experiment 2 equated total ethanol intake in rats trained with two combinations of flavor quality and ethanol concentration. The Sweet5 group drank flavors with 0.2% saccharin throughout training and tests and received 5% ethanol when they drank CS+, while the Plain10 group drank unsweetened flavors and the CS+ was paired with 10% ethanol. Despite equal daily ethanol doses, the Sweet5 group strongly preferred the CS+ (89%) while the Plain10 group avoided it (31%). The two groups continued to show opposite CS+ preference profiles even when both were tested with sweet CS flavors and 10% ethanol infusions. Thus, sweet taste contributes to the development of ethanol-conditioned flavor preferences, and this effect is not explained by a simple enhancement of ethanol intake.     

D1 but not D2 dopamine receptor antagonism blocks the acquisition of a flavor preference conditioned by intragastric carbohydrate infusions

The effects of dopamine D1 (SCH23390) and D2 (raclopride) receptor antagonists on the acquisition and expressions of flavor preferences conditioned by the postingestive actions of sucrose were investigated. Food-restricted rats were trained in one-bottle sessions to associate one flavored saccharin solution (CS+) with intragastric (i.g.) infusions of 16% sucrose, and another flavored saccharin solution (CS-) with water infusions. Flavor preferences were then measured in two-bottle tests. In Experiment 1A, rats that received the D2 antagonist (raclopride, 200 nmol/kg; RAC group) throughout training consumed less CS+ and CS- than did saline-treated Control rats; a saline-treated Yoked group had its intake limited to that of the RAC group. All three groups displayed CS+ preferences during two-bottle tests when treated with saline or raclopride, except at doses that greatly suppressed intake. Experiment 1B obtained similar results with rats treated with 400 nmol/kg raclopride throughout training. In Experiment 2, rats that received the D1 antagonist (SCH23390, 200 nmol/kg; SCH group) throughout training consumed less CS+ and CS- than did saline-treated Control rats; a saline-treated Yoked group had its intake limited to that of the SCH group. Unlike the Control and Yoked groups, the SCH group failed to prefer the CS+ to the CS- in two bottle tests. SCH23390 treatment during two-bottle testing did not block CS+ preference in the Control or Yoked groups, except at doses that greatly suppressed intake. We conclude that D1, but not D2, dopamine receptors are critically involved in the acquisition of a sucrose-conditioned flavor preference, and both receptor subtypes have a more limited role in the expression of this preference.     

Pharmacology of flavor preference conditioning in sham-feeding rats: effects of naltrexone.

Relatively little is known about the neurochemical and pharmacological mechanisms involved in flavor preference learning. The present study examined the ability of the opioid antagonist, naltrexone to alter the acquisition and expression of flavor preferences conditioned by the sweet taste of sucrose. This was accomplished by adding a novel flavor (the CS+) to a sucrose solution, and a different flavor (the CS-) to a less-preferred saccharin solution. Rats were trained to drink these solutions with an open gastric fistula (sham-feeding), which minimized postingestive actions. Food-restricted (Experiments 1 and 2A) and ad lib-fed (Experiment 2B) rats were given either limited (Experiment 1) or unlimited (Experiment 2) access to the CS+ and CS- solutions during one-bottle training. Preferences were assessed in two-bottle tests (with the CS+ and CS- flavors presented in mixed sucrose-saccharin solutions) following vehicle or naltrexone (0.1-10 mg/kg, SC) treatment. The rats displayed significant CS+ preferences following vehicle, particularly after unlimited access training. In four of five experiments, naltrexone significantly reduced total intakes during the two-bottle, sham-feeding tests. Except for one instance, however, the drug failed to block the preference for the CS+ flavor over the CS- flavor. The effects of naltrexone (0.1 mg/kg) on the acquisition of flavor preferences were studied in sham-feeding rats under limited (Experiment 3A) and unlimited (Experiment 3B) training access conditions. Rats treated with naltrexone during training displayed similar CS+ preferences as did saline-treated rats, even though they consumed less CS+ during training. The naltrexone-trained rats also displayed smaller reductions in total or CS+ intakes than did saline-trained rats when all rats were treated with a 2.5 mg/kg dose of naltrexone during testing. As in previous studies, these results show that naltrexone significantly reduces the intake of sweet solutions, yet it has little or no effect on the acquisition or expression of flavor preferences conditioned by sucrose in sham-feeding rats.     

Naltrexone does not prevent acquisition or expression of flavor preferences conditioned by fructose in rats

The effects of the general opioid antagonist, naltrexone, on the acquisition and expression of flavor preferences conditioned by the sweet taste of fructose were examined. Food-restricted rats were trained over eight daily alternating one-bottle sessions (2 h) to drink an 8% fructose solution containing one novel flavor (CS+/F) and a less preferred 0.2% saccharin solution containing a different flavor (CS-/S). Four groups of rats were treated daily with either saline (control group) or naltrexone doses of 0.1, 1.0, or 5.0 mg/kg during training. Preferences were assessed in two-bottle tests with the CS+/S and CS-/S flavors presented in 0.2% saccharin solutions following saline injections. Naltrexone dose-dependently reduced fructose and saccharin intakes during training, confirming the drug's well-known suppressive effect on the intake of sweet solutions. Despite their reduced training intakes, the naltrexone groups displayed preferences for the CS+/S over the CS-/S (72-86%) that were similar to that of the control group (78%). The effect of naltrexone on the expression of the CS+/S flavor preference was evaluated by treating control rats with naltrexone (0.1-5 mg/kg) prior to CS+/S vs. CS-/S choice tests. The drug doses produced a dose-dependent reduction in CS+/S intake but did not significantly attenuate the CS+/S preference. These data are consistent with the relative inability of naltrexone to reduce flavor-flavor conditioning by sucrose in sham-feeding rats and flavor-nutrient conditioning in rats receiving intragastric sucrose infusions. In contrast, dopamine antagonists reduce both sucrose- and fructose-conditioned flavor preferences, which indicates the sensitivity of these conditioning paradigms to neuropharmacological manipulations. These data indicate that the endogenous opioid system, unlike the dopamine system, does not play a major role in either the acquisition or expression of flavor preference learning as measured in two-bottle choice tests.     

Role of systemic endocannabinoid CB-1 receptor antagonism in the acquisition and expression of fructose-conditioned flavor-flavor preferences in rats

Rats learn to prefer a flavor mixed into a fructose-saccharin solution over a different flavor mixed into a saccharin-only solution which is considered to be a form of flavor-flavor conditioning. Fructose-conditioned flavor preferences are impaired by systemic dopamine D1 and to a lesser degree, D2 receptor antagonism as well as by NMDA, but not opioid, receptor antagonism. Given the emerging role of the endocannabinoid system in mediating hedonically-driven food intake, the present study examined whether systemic administration of the inverse CB-1 receptor agonist, AM-251 would alter fructose-conditioned flavor preferences. In Experiment 1, food-restricted rats were trained over 10 sessions (30 min/day) to drink a fructose-saccharin solution mixed with one flavor (CS+/Fs) and a less-preferred saccharin-only solution mixed with another flavor (CS-/s). Subsequent two-bottle tests with the two flavors in saccharin (CS+/s, CS-/s) occurred 15 min following counterbalanced pairs of AM-251 doses of 0, 0.1, 1 or 3 mg/kg. Preference for CS+/s over CS-/s following vehicle treatment (74%) was significantly reduced by the 0.1 (67%) and 1 (65%) AM-251 doses, whereas CS+/s, but not CS-/s intake was significantly reduced by the 1 and 3 mg/kg AM-251 doses. In Experiment 2, rats received systemic injections of AM-251 (1 mg/kg) or vehicle prior to the 10 CS+/Fs and CS-/s training sessions. In subsequent two-bottle tests (drug-free) the AM-251 and control groups displayed similar preferences for the CS+ flavor (66% vs. 69%). Experiment 3 demonstrated that AM-251 significantly decreased chow intake (24 h), and 1-h intakes of fructose-saccharin and saccharin-only solutions in ad libitum-fed rats. These data indicate that functional CB-1 receptor antagonism significantly reduces the expression, but not the acquisition of fructose-conditioned flavor-flavor preferences. The endogenous endocannabinoid system is therefore implicated in the maintenance of this form of learned flavor preferences.     

Classically conditioned motor effects do not occur with cocaine in an unbiased conditioned place preferences procedure

Classical conditioning and behavioural sensitisation of motor activity induced with cocaine (10mg/kg, i.p.) were examined using an unbiased two-compartment conditioned place preference (CPP) procedure. Habituation of the rats to the testing environment prior to training was varied (i.e. either the rats were habituated to the environment for three 30min sessions or they were not) in order to examine a possible influence of latent inhibition on conditioned locomotion or behavioural sensitisation. Furthermore, rats were either trained with an explicit CS+ (cocaine-paired compartment) and CS- (vehicle-paired compartment), or else they were trained with no barrier between the compartments (effectively a single-compartment procedure with no explicit CS-) in order to examine a possible influence of stimulus change (training rats while confined to one compartment, but testing with no barrier between compartments). On a drug-free test day with free access to both compartments, rats previously exposed to cocaine in one compartment (CS+) and vehicle in the second compartment (CS-) spent more time in the CS+ compartment (conditioned place preference). However, under no circumstance was the rate of motor activity higher in the CS+ compartment than in the CS- compartment, as would be expected if cocaine-induced motor activity was classically conditioned to contextual cues. Whether or not increased activity extinguished with repeated drug-free exposures to previously drug-paired contexts depended on habituation experience. In addition, both habituation and current access to compartments (free or restricted) determined the presence of post-extinction sensitisation to a challenge dose of cocaine (7.5mg/kg). Classical conditioning and non-associative sensitisation, independently or together, cannot account for this pattern of results.     

Dopamine D1 and D2 antagonists reduce the acquisition and expression of flavor-preferences conditioned by fructose in rats

The effects of dopamine (DA) D(1) and D(2) receptor antagonists on the acquisition and expression of flavor-preferences conditioned by the sweet taste of fructose were examined. Food-restricted rats were trained over eight alternating one-bottle sessions to drink an 8% fructose solution containing one novel flavor (CS+) and a less preferred 0.2% saccharin solution containing a different flavor (CS-). Three groups of rats were treated daily with either vehicle (control group), SCH23390 (200 nmol/kg; D(1) group), or raclopride (200 nmol/kg; D(2) group) during training. Additional groups of vehicle-treated rats had their daily training intakes matched to that of the D(1) and D(2) groups. Preferences were assessed in two-bottle tests with the CS+ and CS- flavors presented in 0.2% saccharin solutions following doses of 0, 50, 200, 400, or 800 nmol/kg of either D(1) or D(2) antagonists. The D(1) and D(2) groups, unlike the control and yoked-control groups, failed to display a significant CS+ preference in the two-bottle tests following vehicle treatment. In addition, treatment with SCH23390 prior to the two-bottle tests blocked the expression of the CS+ preference in the control groups. Pretest raclopride treatment attenuated the CS+ preference at some dose levels. Raclopride also attenuated the preference for fructose in rats given two-bottle training with the CS+/fructose (CS+/F) and CS-/saccharin (CS-/S) solutions. These findings indicate that D(1) and D(2) antagonists block flavor-preference conditioning by sweet taste and that D(1), and to a lesser extent D(2), receptor antagonists attenuate the expression of a previously acquired preference.     

Pharmacology of flavor preference conditioning in sham-feeding rats: effects of dopamine receptor antagonists

Opioid and dopamine systems are both implicated in the response to sweet solutions. Our laboratory previously reported that the opioid antagonist, naltrexone, reduced the intake of sweet solutions, yet had little or no effect on sucrose-conditioned flavor preferences in sham-feeding rats. The present study examined the role of dopamine D(1) and D(2) receptors in the expression of flavor preferences conditioned by the sweet taste of sucrose. All sessions were conducted under sham-feeding conditions to minimize postingestive influences. Training was accomplished by adding a novel flavor (CS+) to a 16% sucrose solution, a different flavor (CS-) to a less-preferred 0.2% saccharin solution in alternating, one-bottle sessions. Preferences were assessed in two-bottle tests with the CS+ and CS- flavors presented in mixed sucrose (8%)-saccharin (0.1%) solutions following systemic doses of 0, 50, 200, 400, or 800 nmol/kg of the D(2) antagonist, raclopride (Experiment 1) or the D(1) antagonist, SCH23390 (Experiment 2) under either food-restricted or unrestricted conditions. Rats significantly preferred the CS+ solutions in vehicle tests, and displayed equipotent and dose-dependent reductions in total intake and CS+ preference following either D(1) or D(2) receptor antagonism. Similar results were obtained with SCH23390 and raclopride in Experiment 3 conducted with water-restricted rats. These data indicate that dopaminergic D(1) and D(2) receptors play pivotal and functionally equivalent roles in the expression of flavor preferences conditioned by the sweet taste of sucrose.     

The effects of midazolam on the acquisition and expression of fructose- and maltodextrin-based flavour preferences

The effects of the benzodiazepine agonist midazolam on the acquisition and expression of flavour preferences were investigated. Rats (Experiment 1) were given one-bottle training with one flavoured solution (CS+) mixed with either fructose or maltodextrin and another solution (CS-) presented alone. Animals receiving 1 mg/kg midazolam during training consumed more CS- than did animals receiving vehicle injections although there was no drug effect on CS+ consumption. In two-bottle tests the CS+ was preferred to the CS- with the preference being larger in fructose trained animals. Midazolam (0.3-3 mg/kg) increased total intake but not CS+ preference. Training under midazolam reduced the CS+ preference when fructose, but not maltodextrin, was the reinforcer. In Experiment 2 training consumption was restricted to 10 ml/session. This removed the difference in CS+ preference between reinforcer types but otherwise the results were as in Experiment 1. The midazolam induced attenuation of fructose-based preferences might reflect an increase in CS- palatability during training which would reduce the difference between the reinforced and non-reinforced solutions. As maltodextrin supports preferences due to post-ingestive effects manipulation of palatability should be ineffective. Midazolam does not influence the expression of conditioned flavour preferences despite prior evidence that benzodiazepine agonists enhance palatability.     

Conditioned activation induced by ethanol: role in sensitization and conditioned place preference.

Previous studies of ethanol-induced activation and place preference conditioning have shown that repeated exposure to ethanol produces sensitization to ethanol's locomotor activating effect in mice. This experiment was designed to determine whether the behavioral sensitization to ethanol that occurs during place preference conditioning is due to development of a Pavlovian conditioned activity response. Mice (DBA/2J) in the experimental group (BEFORE) received four pairings of a distinctive floor stimulus with ethanol (2 g/kg, IP); a different floor stimulus was paired with saline (counterbalanced). Mice in two control groups were exposed equally to each floor stimulus and were handled and injected as often as experimental mice. One control group (AFTER) always received ethanol in the home cage 1 h after exposure to the floor stimulus, while the other control group (NO-DRUG) never received ethanol during conditioning. BEFORE group mice showed a significant conditioned place preference, whereas control mice did not. Activity tests after saline or ethanol indicated higher activity levels in BEFORE mice compared to control mice, regardless of floor stimulus. Moreover, BEFORE mice were more active on their CS+ floor than on their CS- floor during saline tests; activity was equally elevated on both floors during ethanol tests. These results support the hypothesis that sensitization to ethanol's activating effect is mediated by Pavlovian conditioning. Further, they suggest that place conditioning established-associative control by two kinds of stimuli; the specific tactile cues serving as CS+ and CS- and the general environmental cues common to both CS+ and CS- trials.(ABSTRACT TRUNCATED AT 250 WORDS)     

Flavor preference conditioning by oral self-administration of ethanol

 Oral self-administration and operant tasks have been used successfully to confirm ethanol′s positive reinforcing effects in rats. However, in flavor conditioning tasks, ethanol is typically found to have aversive effects. The present studies explored this apparent paradox by examining the change in value of a flavor paired with orally self-administered ethanol in two different limited-access procedures. Rats were food-deprived and trained to drink (experiment 1) or to barpress for (experiment 2) 10% (v/v) ethanol during daily 30-min sessions using prandial initiation techniques. All rats were then exposed to a differential flavor conditioning procedure in which banana or almond extract was added to the drinking solution. One flavor (counterbalanced) was always mixed with ethanol (CS+), whereas the other flavor was mixed with water (CS–). By the end of conditioning, rats in both experiments drank more flavored ethanol than flavored water, confirming ethanol’s efficacy as a reinforcer. Moreover, barpress rates for CS+ exceeded those for CS– in the operant task. Ethanol doses self-administered in final sessions averaged about 1 g/kg. The effect of the flavor-ethanol contingency was assessed in preference tests that offered a choice between the two flavor solutions without ethanol. In both experiments, subjects developed a preference for the flavor that had been paired with ethanol. Thus, the outcome of flavor conditioning was consistent with that of the oral self-administration tasks in providing evidence of ethanol’s rewarding effects. These experiments confirm and extend previous studies showing that flavor aversion is not the inevitable result of flavor-ethanol association in rats. It seems likely that ethanol’s nutrient and pharmacological effects both contributed to the development of conditioned flavor preference. Received: 15 February 1997 / Final version: 11 June 1997     

Effects of prenatal ethanol exposure on avoidance conditioning in high-and low-avoidance rat strains

Two lines of rats selected for high-and low-avoidance performance consumed a nutritions liquid diet containing 35% ethanol-derived calories through days 5–18 of gestation. Control dams were pair-fed an identical liquid diet except for isocaloric substitution of sucrose for ethanol or ad libitum laboratory chow and water. Subsequently, the offspring of the low-avoider dams fed ethanol were found to be impaired on two-way shock-avoidance conditioning when compared to the pair-fed and ad libitum controls from the same line. In contrast, the offspring of the high-avoider dams fed ethanol displayed similar levels of avoidance, responding to their controls. These results demonstrate that the effects on avoidance conditioning of in utero ethanol exposure are dependent upon the line of rat studied.     

Effect of addition of ethanol and NaCl on saccharin + glucose polydipsia.

Rats received an ad lib choice of food, water, and a solution containing saccharin, glucose, and NaCl solutes either as single stimuli or in combinations. Ethanol was gradually added to these vehicles or water from 0.5--15% w/v. Ethanol intakes of all groups with vehicles containing glucose were higher than intakes of the water vehicle group. Ethanol intakes of the 0.125% saccharin + 3.0% glucose + 1.0% NaCl + ethanol group were highest, peaking at greater than 9.0 g/kg/day, and this group displayed the highest blood ethanol levels. However, there was no evidence of withdrawal syndrome, nor of increased intake of unflavored ethanol by groups previously receiving flavored ethanol. It is suggested that ethanol eliminative capacity limits free-choice ethanol intake when maximized by the addition of sapid congeners.     

Baclofen alters ethanol-stimulated activity but not conditioned place preference or taste aversion in mice.

The present experiments examined the effects of the GABA(B) receptor agonist, baclofen, on the acquisition of ethanol-induced conditioned place preference (CPP) and conditioned taste aversion (CTA) in male DBA/2J mice. Mice in the CPP experiment received four pairings of ethanol (2g/kg) with a distinctive floor stimulus for a 5-min conditioning session (CS+ sessions). On intervening days (CS- sessions), mice received saline injections paired with a different floor type. On CS+ days, mice also received one of four doses of baclofen (0.0. 2.5, 5.0, or 7.5 mg/kg) 15 min before an injection of ethanol. For the preference test, all mice received saline injections, and were placed on a half-grid and half-hole floor for a 60-min session. Baclofen dose dependently reduced ethanol-stimulated activity, but did not alter the magnitude of ethanol-induced CPP at any dose. For the CTA experiment, mice were adapted to a 2-h per day water restriction regimen followed by five conditioning trials every 48 h. During conditioning trials, subjects received an injection of saline or baclofen (2.0 and 6.0 mg/kg) 15 min before injection of 2 g/kg ethanol or saline following 1-h access to a saccharin solution. Baclofen did not alter the magnitude of ethanol-induced CTA at any dose. In addition, baclofen alone did not produce a CTA. Overall, these studies show that activation of GABA(B) receptors with baclofen reduces ethanol-induced locomotor activation, but does not alter ethanol's rewarding or aversive effects in the CPP and CTA paradigms in DBA/2J mice.     

Opioid receptor antagonism in the nucleus accumbens fails to block the expression of sugar-conditioned flavor preferences in rats

In our prior studies, systemic administration of the opioid receptor antagonist naltrexone (NTX) did not block flavor preference conditioning by the sweet taste or post-oral actions of sugar despite reducing intake. Because opioid signaling in the nucleus accumbens (NAc) is implicated in food reward, this study determined if NTX administered into the NAc would block the expression of sugar-conditioned preferences. In Experiment 1, food-restricted rats with bilateral NAc shell or core cannulae were trained to drink a fructose (8%) + saccharin (0.2%) solution mixed with one flavor (CS+) and a less-preferred 0.2% saccharin solution mixed with another flavor (CS−) during one-bottle sessions. Two-bottle tests with the two flavors mixed in saccharin solutions occurred 10 min following total bilateral NAc shell or core doses of 0, 1, 25 and 50 μg of NTX. The rats preferred the CS+ over CS− following vehicle (80%) and all NTX doses in the shell and core. The CS+ preference was reduced to 64% and 72% by 50 μg NTX in the shell and core, although only the core effect was significant. In Experiment 2, food-restricted rats were trained to drink one flavored saccharin solution (CS+) paired with an intragastic (IG) glucose (8%) infusion and a second flavored saccharin solution (CS−) paired with an IG water infusion. In subsequent two-bottle tests, the rats displayed significant preferences for the CS+ (81-91%) that were unaltered by any NTX dose in the shell or core. CS+ intake, however, was reduced by NTX in the shell, but not the core. These data indicate that accumbal opioid antagonism slightly attenuated, but did not block the expression of sugar-conditioned flavor preferences. Therefore, while opioid drugs can have potent effects on sugar intake they appear less effective in altering sugar-conditioned flavor preferences.     

Second-order (environmental) conditioning of a taste aversion in rats

Four groups of rats (n = 10/group) were conditioned in a taste aversion task using a second-order reinforcer associated with precipitated morphine withdrawal. Rats in CS+, CS- and CS(random) groups were exposed to a chronic morphine (morphine sulfate, MS) dosing regimen. A control group received equivalent volumes of saline. All rats then received daily i.p. injections of naloxone HCI (1.0-3.2mg/kg), inducing precipitated morphine withdrawal in group-dependent unique environments. The 4-h withdrawal trials were terminated by a 20mg/kg MS injection (MS treatment groups only) and returned to their home cage. After a 1-week wash-out was imposed, all subjects were exposed to a conditioned taste aversion (CTA) task using environmental stimuli (CSI) from Phase 1 paired with saccharin (CS2) in a second-order conditioning procedure. The CS+ group developed a significant CTA; the CS- and CS(random) groups increased their consumption of saccharin. The saline group was unaffected by the treatment conditions. The data demonstrate the salience and importance of environmental stimuli and suggest a role for such conditioning in drug relapse phenomena.     

Opioid mediation of starch and sugar preference in the rat

In our prior studies, administration of the opioid receptor antagonist naltrexone did not block conditioned preferences for a flavor paired with a preferred sugar solution over a flavor paired with saccharin. This may be because both training solutions were sweet, and their attractiveness was reduced by naltrexone. The present study compared the effects of naltrexone on preferences for flavors paired with sugar or starch drinks that have distinctive tastes to rats. Experiment 1 assessed naltrexone's effect on the preference for unflavored 8% cornstarch and 8% sucrose aqueous solutions/suspensions. The food-restricted rats displayed a significant sucrose preference which increased following systemic treatment with naltrexone (1 or 3 mg/kg) even though total intake of both solutions declined. In Experiment 2, rats were trained to drink flavored (cherry or grape) starch and sucrose solutions in separate one-bottle sessions. In a two-bottle choice test with both flavors presented in a sucrose-starch mixture, the rats significantly preferred the starch-paired flavor. Naltrexone treatment blocked the expression of this starch-conditioned preference. In Experiment 3, rats were treated with saline or naltrexone throughout one-bottle training with flavored sucrose and starch solutions. In a subsequent choice test, both the saline and naltrexone groups displayed significant preferences for the starch-paired flavor, indicating that opioid antagonism failed to alter the acquisition of this conditioned preference. In summary, novel outcomes of this study included the increased rather than the predicted decrease in sucrose preference produced by naltrexone. Also, starch unexpectedly conditioned the stronger flavor preference, although this can be explained by the differential post-oral reinforcing actions of starch and sucrose, and naltrexone blocked the expression, but not the acquisition, of this preference. These findings suggest that the reward value of starch in liquid form is more dependent upon opioid signaling than is that of sugar.     

Ethanol flavor preference conditioned by intragastric carbohydrate in rats

The unpalatable flavor of ethanol solutions greater than approximately 6% may limit their consumption by rats. We determined if ethanol flavor avoidance, like bitter or sour taste avoidance, can be reversed by intragastric (IG) carbohydrate conditioning. Ad lib fed rats drank 5% ethanol and a matched flavor (0.05% citric acid+0.5% maltodextrin, CM) on alternate days. For control rats, postingestive effects were equated: when they drank one solution they were infused IG with the other. Conditioned rats were also infused with 5% ethanol when they drank CM, but when they drank 5% ethanol they were infused with CM + 16% maltodextrin, a potent reward in flavor preference learning. In choice tests, only the conditioned rats preferred ethanol to CM; both groups preferred 5% ethanol to water. Conditioned rats but not controls preferred ethanol to water when the concentration was raised to 10%, and sustained their preference when the infusate carbohydrate was gradually removed. When ethanol concentration was gradually raised to 25%, ethanol preference declined from 48% to 30% in the control rats and from 84% to 50% in the conditioned rats. Thus, ethanol flavor avoidance can be reversed or reduced by postingestive nutritive conditioning, which may combine with the pharmacological effects of ethanol to produce the acquired appetite for the flavor of alcoholic beverages.