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.     

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.     

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.     

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.     

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 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.     

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.     

Double-dissociation of D1 and opioid receptor antagonism effects on the acquisition of sucrose-conditioned flavor preferences in BALB/c and SWR mice

Sugar appetite is influenced by unlearned attractions to sweet taste and learned responses to sugars' taste and post-ingestive actions. In rats, sugar-conditioned flavor preferences (CFP) are attenuated by dopamine D1 (SCH23390: SCH), but not by opioid (naltrexone: NTX), receptor antagonism. Sucrose-CFP occurs in BALB/c and SWR inbred mice that differ in their suppressive effects of SCH and NTX on sucrose intake. The present study examined whether SCH and NTX altered expression of previously learned sucrose-CFP and acquisition (learning) of sucrose-CFP in these strains. In Experiment 1, food-restricted mice were trained (10 one-bottle sessions) to drink a more-preferred flavored (e.g., cherry) 16% sucrose solution (CS +/Sucrose) on odd-numbered days, and a less-preferred flavored (e.g., grape) 0.05% saccharin solution (CS −/Saccharin) on even-numbered days. Two-bottle tests with the flavors mixed in 0.2% saccharin occurred 30 min following vehicle (Veh), SCH (50-800 nmol/kg) or NTX (1-5 mg/kg) assessing preference expression. CS + preference expression in BALB/c and SWR mice following Veh were significantly reduced by SCH and NTX. In Experiment 2, separate groups of BALB/c and SWR mice received Veh, SCH (50 nmol/kg) or NTX (1 mg/kg) injections 30 min prior to daily one-bottle training sessions with the CS +/Sucrose and CS −/Saccharin solutions assessing preference acquisition. Subsequent two-bottle tests with the CS + vs. CS − solutions were conducted without injections. CS +/Sucrose training intakes were reduced by SCH in both strains and by NTX in BALB/c mice. In the initial two-bottle test, sucrose-CFP acquisition was significantly reduced in BALB NTX (54%), but not in BALB SCH (77%) groups relative to the BALB Veh group (85%). In contrast, sucrose-CFP acquisition was significantly reduced in SWR SCH (61%), but not in SWR NTX (83%) groups relative to the SWR Veh group (86%). DA D1 and opioid receptor signaling modulate acquisition and/or expression of sucrose-CFP in mice with significant strain differences observed.     

Pharmacology of sucrose-reinforced place-preference conditioning: effects of naltrexone

Two experiments investigated the role of the opioid system in sucrose-reinforced conditioned place preferences (CPPs) in rats. Experiment 1 examined the effects of a general opioid antagonist, naltrexone, on the expression of a CPP acquired in the absence of the drug. Subjects were trained to associate one compartment of a two-compartment chamber with sucrose and the other compartment with water. Rats displayed a preference for the sucrose-associated compartment in a choice test without sugar or water available following vehicle saline treatment. Naltrexone doses of 2.5 and 5.0 mg/kg reduced this preference for the sucrose-associated compartment. Experiment 2 examined the effects of naltrexone on the acquisition as well as the expression of CPPS. Different groups of rats received daily injections of either saline, 0.1, 1.0, or 5.0 mg/kg of naltrexone prior to each training session, and then these groups were given a choice test for the CPP after saline or naltrexone injections. Although naltrexone treatment attenuated the expression of CPPs in each group relative to saline treatment, there were no group differences during these tests in the magnitude of the preferences. Moreover, all groups displayed equal acquisition of CPPs despite the fact that naltrexone dose dependently decreased sucrose intake during the training phase. Together, the results indicate that the opioid system modulates the expression but not the acquisition of sucrose-reinforced CPPs.     

Rewarding and aversive effects of morphine: Temporal and pharmacological properties

To assess morphine-induced location preferences and flavor aversions, rats were administered morphine sulfate (10 mg/kg, IP) either immediately before (Experiment 1) or immediately after (Experiment 2) confinement for 20 min in one side of a shuttlebox with access to a flavored solution. On control trials the rats were administered saline and confined for 20 min on the opposite side with a differently flavored solution. In subsequent choice tests, it was found that morphine injections before confinement produced a preference for the side associated with morphine and indifference to the flavors, whereas morphine injections after confinement produced an aversion to the flavor paired with morphine and indifference to the sides. Experiments 3 and 4, using a procedure similar to that of Experiment 1, showed that naloxone (1 mg/kg, IP) blocked the morphine-induced side preference, although given alone it was without effect in this test.     

Flavor preferences conditioned by intragastric infusion of ethanol in rats

Sprague-Dawley rats were trained 22 h/day to associate a flavored solution [conditioned stimulus (CS+)] with intragastric infusions of 6% ethanol and another flavored solution (CS-) with water infusions. The infusions were matched to the CS intakes so that the animals determined their timing and size. In Phase 1, chow and water were available ad libitum, and both CS flavors were initially sweetened with saccharin that was then faded out. The rats displayed a preference for the CS+ over the CS- under both reinforced and extinction conditions. When food-restricted in Phase 2, the rats displayed an increased preference for the CS+. In Phase 3, the rats were fed ad libitum chow and given preference tests with the CS+ paired with ethanol infusions of increasing concentration (6%, 12%, 18%, and 24%). Their preference for the CS+ over the CS- persisted, and self-administered ethanol dose increased with concentration to 5 g/kg/day. The ethanol-based conditioned flavor preference resembled those conditioned by carbohydrate and fat infusions, suggesting that at least some of reinforcing ability of ethanol may be related to its postingestive nutritive effects.     

Chin rub CRs are elicited by flavors associated with apomorphine, scopolamine, methscopolamine, physostigmine and neostigmine

Three experiments were conducted in order to determine the pattern of behavioral conditioned responses (CRs) elicited by flavors paired with each of various drugs which effectively establish avoidance of a flavored solution. Each of the drugs employed supported both chin rub CRs and avoidance of a flavored solution. Experiment 1 employed apomorphine, a classic emetic agent which pharmacologically acts as a dopaminergic agonist. Experiment 2 and 3 employed cholinergic agonists and antagonists which were either peripherally or both peripherally and centrally acting agents. The results suggest that chin rub CRs may be produced by means of the activation of a system which is peripheral to the CNS. Furthermore, flavor avoidance produced by drugs which support chin rub CRs may be mediated by a shift in the hedonic rating of the flavored solution; whereas, flavor avoidance produced by drugs which do not support chin rub CRs is probably mediated by a mechanism other than a hedonic shift.     

Role of D(1) and D(2) dopamine receptors in the acquisition and expression of flavor-preference conditioning in sham-feeding rats

The present study examined the effects of D(1) and D(2) antagonists on flavor-preference conditioning by the sweet taste of sucrose. All sessions were conducted under sham-feeding conditions to minimize post-ingestive influences. The rats were trained in alternating, one-bottle sessions to sham-feed a 16% sucrose solution containing one novel flavor (CS+) and a less-preferred 0.2% saccharin solution containing a different flavor (CS-). Three groups of food-restricted rats were treated with either vehicle (control group), the D(1) antagonist, SCH23390 (200 nmol/kg), or the D(2) antagonist, raclopride (200 nmol/kg) during one-bottle training. A fourth group (yoked group) was vehicle-treated and its training intakes were matched to that of the D(1) and D(2) drug groups. Preferences were assessed in two-bottle tests with the CS+ and CS- flavors presented in mixed 8% sucrose+0.1% saccharin solutions following systemic doses of 0, 200, or 800 nmol/kg of either the D(1) or D(2) antagonists. All groups significantly preferred the CS+ flavor in vehicle tests, although the preferences were weaker in the D(1), D(2), and yoked groups compared to the control group. All groups selectively reduced their CS+ intakes when treated with either D(1) or D(2) antagonists during two-bottle testing, and the CS+ preference was blocked at the higher doses. These data show that D(1) and D(2) receptor antagonists block the expression of a sucrose-conditioned preference, but produces substantially lesser effects upon the acquisition of this form of flavor conditioning.     

Naltrexone suppresses the late but not early licking response to a palatable sweet solution: opioid hedonic hypothesis reconsidered

Opioid antagonists suppress the intake of sweet solutions, but typically have little effect on the initial rate of drinking. The lack of an early drug response was investigated in the present study because it questions the general idea that opioid antagonists reduce the hedonic response to sweets. The first experiment, which measured the rat's licking response to a sucrose+saccharin (S+s) solution, revealed that naltrexone suppressed S+s intake but not initial lick rates. Experiment 2A indicated that the drug's delayed behavioral effect was not due to the 10-min injection-test interval used. Increasing the interval to 20 min did not reduce the latency of drug action. Experiment 2B tested the idea that rats require several minutes to detect that naltrexone has reduced the hedonic value of the S+s solution. The S+s solution was presented either for 30 min without interruption or for 3 min followed, after a 6-min delay, by another 27-min access. In both test conditions, naltrexone did not suppress S+s licking until 7-9 min of drinking had occurred. However, the drug blocked an "appetizer effect"; a post-delay increase in licking rate produced by the split-session test procedure. Microstructure analysis indicated that in all cases, naltrexone reduced S+s licking by reducing the number of lick clusters rather than lick cluster size. In contrast to these drug effects, Experiment 2C showed that reducing the concentration of the S+s solution decreased initial lick rates. Together, these findings suggest that opioid antagonists do not affect all aspects of flavor hedonics, but may primarily alter the intake-maintaining action of palatable flavors.     

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     

Flavored electronic cigarette use,preferences, and perceptions in pregnant mothers: A correspondence analysis approach

Use, preferences, and perceptions of flavored electronic cigarettes (e-cigarettes) were investigated in an ethnically diverse sample of pregnant mothers (N = 100; 50% smokers, M_age = 26; 66% low income; 65% minorities) via detailed interviews. Fruit and mint were the most commonly used flavors. Pregnant women endorsed increased use of fruit flavored e-cigarettes in preconception and pregnancy, greater preferences and intentions to use sweet flavors (fruit and candy), and lowest preferences for tobacco flavors. No differences in perceptions of general, pregnancy, or fetal-related health risks emerged across flavors. Latent factor mapping (biplots) based on correspondence analyses of contingency tables revealed clustering of more-preferred fruit and candy flavors versus least-preferred tobacco flavored e-cigarettes, with other sweet flavors—mint and alcohol—clustering more closely with fruit and candy flavors, and more pungent flavors—spice, coffee, chocolate—clustering near tobacco. Correspondence analysis also revealed uncorrelated clustering of preferences and harm perceptions, with intentions showing associations with both preferences and harm perceptions. Preference for fruit and mint flavored e-cigarettes and decreased harm perceptions significantly differentiated lifetime e-cigarette users from non-users. Results highlight preferences for fruit and mint flavored e-cigarettes during preconception and pregnancy, and links between preferences for fruit and mint flavors and lifetime use of e-cigarettes. These findings also highlight the utility of correspondence analysis for elucidating clustering of flavor perceptions and preferences for novel tobacco products.     

Defensive burying of flavors paired with lithium but not amphetamine

Although rats demonstrated avoidance of both lithium- and amphetamine-paired flavored solutions, only the lithium-paired flavor elicited a defensive burying response. These data support the contention that lithium-paired flavors become hedonically unpalatable. Additionally, a simplified economical method for measuring defensive burying is described.     

Effects of a low dose of naltrexone on glucose-induced allesthesia and hunger in humans

In order to study the effects of a low dose of the opioid antagonist naltrexone on ingestive behavior for sucrose in humans, preference for sucrose solutions and feelings of hunger were scored on visual analogical scale by 14 healthy subjects with or without naltrexone. Effects of intragastric glucose load or water, and naltrexone (25 mg) or placebo were tested. At this low dose, naltrexone alone had a slight effect on allesthesia, and it produced a strong potentiation of glucose-induced allesthesia.     

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.