Parabrachial lesions in rats disrupt sodium appetite induced by furosemide but not by calcium deprivation.

An appetite for CaCl2 and NaCl occurs in young rats after they are fed a diet lacking Ca or Na, respectively. Bilateral lesions of the parabrachial nuclei (PBN) disrupt normal taste aversion learning and essentially eliminate the expression of sodium appetite. Here we tested whether similar lesions of the PBN would disrupt the calcium-deprivation-induced appetite for CaCl2 or NaCl. Controls and rats with PBN lesions failed to exhibit a calcium-deprivation-induced appetite for CaCl2. Nevertheless, both groups did exhibit a significant calcium-deprivation-induced appetite for 0.5M NaCl. Thus, while damage to the second central gustatory relay in the PBN disrupts the appetite for 0.5M NaCl induced by furosemide, deoxycorticosterone acetate, and polyethylene glycol, the sodium appetite induced by dietary CaCl2 depletion remains intact.

Parabrachial nucleus lesions block taste and attenuate flavor preference and aversion conditioning in rats.

Rats with ibotenic acid lesions of the parabrachial nucleus (PBN) failed to learn a taste aversion induced by lithium chloride (LiCl) toxicosis. The same rats also did not learn to prefer a taste that was paired with intragastric (IG) carbohydrate infusions during 22 hr/day trials. The PBN-lesioned rats did learn to prefer a flavor (odor + taste) paired with the IG carbohydrate infusions over a different flavor paired with IG water. The PBN-lesioned rats also learned to avoid a flavor paired with IG LiCl infusions during 22 hr/day trials. The flavor preference and aversion, however, were less pronounced than those displayed by control rats. These data indicate that the PBN is essential for forming orosensory-viscerosensory associations when taste is the primary cue but is less critical when more complex flavor cues are available.

The suppressive effects of intraperitoneal cocaine are augmented when evaluated in nondeprived rats.

Rats suppress intake of a saccharin conditioned stimulus (CS) when paired with all drugs of abuse tested including morphine, cocaine, heroin, amphetamine, and ethanol. Although most of these drugs suppress intake when administered via a range of routes, the efficacy of cocaine is an exception. Specifically, cocaine-induced suppression of saccharin intake is much greater when administered subcutaneously than when administered intraperitoneally. The subcutaneous route of administration of cocaine, however, is somewhat problematic because, unless diluted, can cause stark necrosis. The present study, then, reexamined the effectiveness of intraperitoneal cocaine using less restrictive deprivation regimens that are known to facilitate the expression of the phenomenon. The results showed that, while only a 10- and 20-mg/kg dose of cocaine suppressed intake of the saccharin CS when evaluated in moderately water-deprived rats, all doses tested (i.e., 5, 10, and 20 mg/kg) significantly reduced CS intake when saccharin-cocaine pairings were evaluated in rats maintained on food and water ad libitum. Taken together, these data show that rats will readily avoid intake of a saccharin cue when paired with the intraperitoneal administration of cocaine and that the magnitude of the effect is augmented when examined in a need-free state.

Chronic morphine treatment exaggerates the suppressive effects of sucrose and cocaine, but not lithium chloride, on saccharin intake in Sprague-Dawley rats.

Three experiments examined the effect of chronic morphine treatment on cocaine-, sucrose-, and lithium chloride (LiCl)-induced suppression of saccharin intake in Sprague-Dawley rats. All rats were either water- or food-deprived and then implanted subcutaneously with 1 morphine (75 mg) or vehicle pellet for 5 days. They were then given brief access to 0.15% saccharin and soon thereafter injected with either cocaine (10 mg/kg s.c.), LiCl (0.009 M, 1.33 ml/100 g body weight i.p.), or saline, or, in Experiment 2, given a 2nd access period to either a preferred 1.0 M sucrose solution or the same 0.15% saccharin solution. There was 1 taste-drug or taste-taste pairing per day for a number of days. The results showed that a history of chronic morphine treatment exaggerated the suppressive effects of a rewarding sucrose solution and cocaine but not those of the aversive agent, LiCl. These data provide further support for the reward comparison hypothesis.

Estrogen-induced suppression of intake is not mediated by taste aversion in female rats.

Estrogen treatment can suppress the intake of a previously presented gustatory conditioned stimulus (CS). This finding has been interpreted as an estrogen-induced conditioned taste aversion. However, a distinction must be made between taste aversion and taste avoidance. In particular, tastes are only considered aversive if they elicit a stereotypic behavioral response, otherwise the reduction in intake is classified as an avoidance. Although aversive orofacial responses have been reported in male rats after taste-estrogen pairings, they have not been examined in ovariectomized female rats. The goal of the present investigation, then, was to use similar procedures to determine whether conditioned aversion also mediates the estrogen-induced reduction of intake in female rats. Animals were introduced to a novel 0.1% saccharin solution and immediately thereafter were given a subcutaneous injection of vehicle or estradiol benzoate (10 microg). Responses were assessed using a two-bottle preference test, a one-bottle acceptance test, and a taste reactivity (TR) test. The results confirmed previous reports of a reduced preference for saccharin after saccharin-estradiol pairing using the two-bottle test. The reduction in intake during the one-bottle test, however, was not accompanied by stereotypic aversive responses, such as gaping. Surprisingly, a similar reduction in intake also occurred when using a backward conditioning procedure in which estrogen was injected before, rather than after, CS access. Thus, the present results show that the suppressive effects of estrogen reflect an avoidance, rather than aversion and, moreover, that the reduced intake may be due to an unconditioned, rather than a conditioned, response.

Heroin-induced suppression of saccharin intake in water-deprived and water-replete rats.

Rats suppress intake of a saccharin conditioned stimulus (CS) when paired with an aversive unconditioned stimulus such as lithium chloride. This phenomenon is referred to as a conditioned taste aversion (CTA). Rats also suppress intake of a saccharin CS when paired with a rewarding sucrose solution and when paired with a drug of abuse. Although the suppressive effects of drugs of abuse have long been interpreted as CTAs, evidence suggests that rats may suppress intake of the saccharin CS following taste-drug pairings because they are anticipating the rewarding rather than the aversive properties of the drug. Oddly, however, while all other drugs of abuse tested suppress intake of a gustatory CS, the highly reinforcing drug, heroin, is reportedly ineffective. The present study reexamined this issue in both water-deprived and water-replete rats using procedures that sustain both morphine- and cocaine-induced suppression of CS intake. The results showed that heroin greatly reduced CS intake following saccharin-heroin pairings and that this effect was less variable when assessed in water-replete subjects. When taken with other reports, these data suggest that rats suppress intake of a saccharin CS in anticipation of the availability of all drugs of abuse tested.

The suppressive effects of sucrose and cocaine, but not lithium chloride, are greater in Lewis than in Fischer rats: evidence for the reward comparison hypothesis.

Rats suppress intake of a saccharin conditioned stimulus (CS) when it is paired with an aversive unconditioned stimulus (US), an appetitive US, or a drug of abuse such as morphine or cocaine. It is unclear, however, whether the reduction in intake induced by these drugs is mediated by their aversive or their rewarding properties. The present set of experiments addressed this question by comparing the suppressive effects of a known aversive US (LiCl), a known reinforcing US (sucrose), and a drug of abuse (cocaine) in two strains of rats (i.e., Lewis and Fischer 344 rats) that differ in their preference for rewarding stimuli. The results show that, although both strains readily acquired a LiCl-induced conditioned taste aversion (CTA), the suppressive effects of sucrose and cocaine were robust in the drug-preferring Lewis rats and absent in the Fischer rats. These data argue against a CTA account and in favor of the reward comparison hypothesis.

Morphine-induced suppression of saccharin intake is correlated with elevated corticosterone levels.

Rats suppress intake of a saccharin conditioned stimulus (CS) when paired with a drug of abuse. This phenomenon, however, is not uniform across all subjects and is greater following exposure to stress and in animals that more readily self-administer drugs of abuse. The present study was designed to examine these individual differences in intake suppression following seven saccharin-morphine pairings. Plasma corticosterone also was evaluated both before and after conditioning in order to determine whether the magnitude of CS suppression is, or is not, related to circulating corticosterone levels. The findings indicated that, while all rats were exposed to the same number of saccharin-morphine pairings, only half of these animals actually suppressed intake of the saccharin CS. Moreover, the results showed that greater suppression of CS intake was associated with higher corticosterone levels at test (r=-0.84, P<0.0001). Taken together, the results demonstrate that individual differences affect not only the reduction in CS intake following taste-drug pairings, but also the associated cue-induced elevation in circulating corticosterone.

Bilateral lesions of the gustatory thalamus disrupt morphine- but not LiCl-induced intake suppression in rats: evidence against the conditioned taste aversion hypothesis.

Rats decrease intake of a saccharin conditioned stimulus (CS) when followed by: (1) the administration of an aversive agent such as lithium chloride (referred to as a conditioned taste aversion, CTA); (2) access to a very palatable concentration of sucrose (referred to as an anticipatory contrast effect, ACE); or (3) the administration of a drug of abuse. It is not clear, however, whether the suppressive effects of drugs of abuse are mediated by their aversive or rewarding properties. The present set of experiments addressed this issue by examining the suppressive effects of morphine in rats with a lesion thought to dissociate the two phenomena (i.e., CTA and ACE). The results show that bilateral ibotenic acid lesions of the gustatory thalamus eliminate the suppressive effects of morphine, but fail to disrupt the suppressive effects of the aversive agent, lithium chloride. This pattern of results argues against the CTA account in favor of the reward comparison hypothesis. Specifically, the data suggest that rats suppress intake of a saccharin CS in anticipation of the availability of a preferred drug of abuse and that the gustatory thalamus is essential for this type of reward comparison process.

Water-deprivation prevents morphine-, but not LiCl-induced, suppression of sucrose intake.

Intake of a saccharin-conditioned stimulus (CS) can be suppressed following pairing with an aversive agent such as lithium chloride (LiCl) or x-rays (referred to as a conditioned taste aversion or CTA), a highly rewarding sucrose solution (referred to as an anticipatory contrast effect), or a drug of abuse such as morphine or cocaine. Although the suppressive effects of LiCl and sucrose are clear examples of aversive and appetitive conditioning, respectively, it is not certain which properties (aversive or appetitive) mediate the suppressive effects of drugs of abuse. It is known, however, that the suppressive effects of a rewarding sucrose US are attenuated when using a caloric sucrose CS in food deprived rats, while LiCl induced CTAs are much less effected. Standard CTA testing typically is conducted in water-deprived rather than food-deprived rats and, although LiCl is known to suppress intake of a sucrose CS in water-deprived rats, the suppressive effects of drugs of abuse have not been evaluated under these conditions. The present experiment, then, compared the suppressive effects of a standard dose of morphine (15 mg/kg) and a matched dose of LiCl (0.009 M) on intake of a sucrose CS in water-deprived and free-feeding rats. The results showed that both drugs suppressed intake in free-feeding subjects, but only the aversive agent, LiCl, reduced CS intake in the water-deprived rats. This finding dissociates the suppressive effects of morphine and LiCl and, in so doing, aligns the suppressive effects of morphine with those of an appetitive sucrose US.

The suppressive effects of LiCl, sucrose, and drugs of abuse are modulated by sucrose concentration in food-deprived rats.

Suppression of intake of a gustatory conditioned stimulus (CS) occurs when paired with either an aversive or an appetitive unconditioned stimulus (US). Toxic substances, such as lithium chloride (LiCl), induce conditioned taste aversions while rewarding stimuli, such as high a concentration of sucrose, reduce intake through a comparison process referred to as anticipatory contrast. Drugs of abuse also suppress CS intake, but it is not known whether they do so via their rewarding or aversive properties. Using 0.1, 0.3, or 0.5 M sucrose solutions as the gustatory CS, we compared the suppressive effects of LiCl (5.29 mg/kg), morphine (15 mg/kg), cocaine (10 mg/kg), and a 1.0-M sucrose solution in rats that were food deprived. The doses of the three drugs have been equated in terms of their suppressive effects in water-deprived and free-feeding rats. The results showed that in food-deprived rats the sucrose US failed to suppress intake of any of the sucrose CSs, the drugs of abuse failed to suppress intake of the 0.3 and 0.5-M concentration of sucrose, and LiCl failed to suppress intake of the 0.5-M sucrose solution. When taken together, these findings reveal that the suppressive effects of all USs (aversive, appetitive, and drugs of abuse) can be offset by the use of a caloric CS when evaluated in food-deprived rats.

The parabrachial nucleus is essential for acquisition of a conditioned odor aversion in rats.

Rats with bilateral ibotenic acid lesions of the gustatory zone of the parabrachial nuclei (PBN) failed to acquire a conditioned taste aversion (CTA) in Experiment 1. They also failed to acquire a conditioned odor aversion (COA) when the olfactory cue was presented on an odor disk in Experiment 2 or when it was presented in water in Experiment 3. The failure to acquire the COA was not due to an inability to detect or use olfactory stimuli because the lesioned rats displayed neophobia to a novel odor in Experiment 3 and used an olfactory cue to predict the availability of an aversive capsaicin solution in Experiment 4. Together, the results demonstrate that, as with CTA learning, PBN cell bodies are essential for the establishment of a specific association between an olfactory conditioned stimulus and a lithium chloride unconditioned stimulus.

Ibotenic acid lesions of the parabrachial nucleus and conditioned taste aversion: further evidence for an associative deficit in rats.

Rats with extensive ibotenic acid lesions centered in the gustatory zone of the pontine parabrachial nucleus (PBN) failed to acquire a conditioned taste aversion (CTA) induced by lithium chloride (LiCl) toxicosis (Experiments 1 and 4). This deficit cannot be explained as an inability to either perceive or process gustatory information because lesioned rats that failed to acquire a CTA readily acquired a conditioned flavor preference (Experiment 2). Similarly, the CTA deficit cannot be attributed to an inability to experience or process visceral input because PBN-lesioned rats that failed to acquire a CTA successfully learned an aversion to a trigeminal stimulus, capsaicin, when paired with LiCl-induced illness (Experiment 3). This pattern of results supports the view that cell bodies within the PBN are essential for the associative processes that govern CTA learning.

Reward comparison in chronic decerebrate rats.

The simultaneous contrast paradigm was used to evaluate responsiveness to a low (0.05 M) and a high (0.5 M) concentration of sucrose under two conditions in intact and chronic decerebrate rats. In one condition the low concentration was presented on one day and the high concentration on another. In the other condition presentation of the two concentration was alternated within the same daily session. In each case there was a total of 40 trials/day during which the stimulus was delivered intraorally for 2 s at a rate of 1.5 ml/min with a 30-s intertrial interval. The results showed that the intact rats always licked more for the high than for the low concentration of sucrose but that the magnitude of the effect was larger when given the opportunity to compare the two concentrations within the same daily session. The decerebrate rats produced a similar pattern, but the concentration effect was evident only when the stimuli were alternated within the same daily session. These data stand as the first evidence that the isolated caudal brain stem is adequate for the expression of a behavior that depends on comparison processes involving short-term memory.

Gustatory functions, sodium appetite, and conditioned taste aversion survive excitotoxic lesions of the thalamic taste area.

Rats with bilateral, electrophysiologically guided, ibotenic acid lesions of the gustatory thalamus (THLX) were tested for their ability to perform a variety of taste-guided behaviors. First, in daily 30-min sessions, the rats were given repeated 10-s access periods to a range of concentrations of sucrose, NaCl, or QHCl, plus water. Both the control and the THLX rats exhibited similar concentration-response functions, regardless of hydrational state. Next, on 3 trials, the rats were given 15 min access to 0.3 M l-alanine and then injected with LiCl (0.15 M, 1.33 ml/100 g body weight ip). All rats learned a taste aversion following 1 pairing with LiCl. Finally, on 3 separate occasions, the rats were injected with furosemide, and Na(+)-appetite was evaluated 24 hr later. All rats expressed an equivalent sodium appetite after the first furosemide injection, but only the control rats increased intake of 0.51 M NaCl with repeated sodium depletions. These observations reinforce prior data implying that an intact gustatory thalamus is not necessary for the expression of some taste-guided behaviors.

Conditioned taste aversions and drugs of abuse: a reinterpretation.

A new hypothesis (and supporting data) provides a solution to the 25-year-old paradox whereby positively reinforcing drugs of abuse also support a conditioned taste aversion (CTA). The results show that unlike LiCl-induced CTAs, morphine- and cocaine-induced suppression of conditioned stimulus (CS) intake depends on the rewarding properties of the gustatory CS. This finding argues against the long-standing CTA interpretation in favor of a new reward comparison account. That is, rats decrease intake of a gustatory CS following taste-drug pairings because the value of the CS is outweighed by that of a highly reinforcing psychoactive drug. Suppression of CS intake, then, is a consequence of the well-documented positive reinforcing, rather than the hypothetical aversive, properties of drugs of abuse.

Brainstem lesions and gustatory function: I. The role of the nucleus of the solitary tract during a brief intake test in rats.

Using an automated gustometer, licking behavior in rats was evaluated for a range of concentrations of appetitive and aversive stimuli in rats following electrolytic lesions in the rostral nucleus of the solitary tract (NST). Lesions of the NST flattened the concentration-response function for all gustatory stimuli. They attenuated the concentration-response function for MgCl2, QHCI, and NH(4)Cl by shifting it to the right by 0.5 log unit, attenuated the function for citric acid and Polycose by shifting it to the right by 1.5 log units, and fully eliminated the function for sucrose and NaCl. This failure to respond appropriately, however, was specific to gustatory stimuli because all rats reduced ingestive responding when presented with increasing concentrations of capsaicin, a trigeminal stimulus. Together, the data show that the NST is critical for responding appropriately to changes in intensity of a gustatory, but not a trigeminal, stimulus.

Brainstem lesions and gustatory function: II. The role of the nucleus of the solitary tract in Na+ appetite, conditioned taste aversion, and conditioned odor aversion in rats.

Rats with lesions of the nucleus of the solitary tract (NST) that demonstrated flat concentration-response functions for NaCl and sucrose (T. Shimura, P. S. Grigson, & R. Norgren, 1997) expressed a significant (albeit reduced) salt appetite following sodium depletion, and a normal conditioned taste aversion (CTA) for alanine when paired with lithium chloride-induced toxicosis. Rats with lesions of the NST also could acquire a conditioned odor aversion, but the CTA to alanine was not mediated by odor cues because other rats with NST lesions also demonstrated normal CTA learning even when made anosmic with zinc sulfate. Together, the data suggest that the rostral NST is essential for responding appropriately to increasing concentrations of a tastant, but not for the chemical identification necessary for sodium appetite and CTA learning.

Brainstem lesions and gustatory function: III. The role of the nucleus of the solitary tract and the parabrachial nucleus in retention of a conditioned taste aversion in rats.

Bilateral electrolytic lesions of the nucleus of the solitary tract (NST) or ibotenic acid lesions of the pontine parabrachial nuclei (PBN) failed to disrupt retention of a preoperatively acquired conditioned taste aversion (CTA) to 0.3 M alanine. For both sham- and NST-lesioned rats, the CTA persisted following 3 nonreinforced conditioned stimulus (CS) presentations. For PBN-lesioned rats, retention was more labile. The preoperatively acquired CTA was extinguished by the 3rd nonreinforced CS exposure. When assessed postoperatively using a novel CS, NST-lesioned rats acquired a new CTA, although they were rendered anosmic with zinc sulfate (P. S. Grigson, T. Shimura, & R. Norgren, 1997). Rats with PBN lesions, however, failed to acquire a second CTA postoperatively. Thus, the PBN is essential for the acquisition of a CTA, but neither of the brainstem gustatory nuclei need be intact for the retention of a preoperatively acquired CTA.