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.

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.

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.

Parabrachial nucleus lesions and conditioned taste aversion: evidence supporting an associative deficit.

Three experiments examined the conditioned taste aversion (CTA) deficit that occurs following electrolytic lesions of the parabrachial nucleus (PBN). In Experiment 1, lesioned rats failed to avoid either a gustatory or an olfactory stimulus that had been paired with lithium chloride-induced toxicosis. In Experiment 2, however, all rats learned a conditioned flavor preference. Finally, in Experiment 3, all controls and 7 of the 12 lesioned rats learned a conditioned place aversion. Together, these results demonstrate that the disruption of CTA in lesioned rats cannot be ascribed to an inability to process either gustatory or visceral afferent information per se. Rather, the data suggest that PBN-lesioned rats are unable to form a specific association between gustatory and visceral cues.

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.

Lesions of the pontine parabrachial nuclei eliminate successive negative contrast effects in rats.

Rats shifted from a high to a low concentration of sucrose make fewer licks for the low concentration than rats that experience only the low concentration of sucrose. This phenomenon, referred to as successive negative contrast, is eliminated after bilateral electrolytic lesions of the amygdala. Because the amygdala receives direct projections from the gustatory zone of the parabrachial nuclei of the pons (PBN), this experiment was designed to examine this phenomenon in rats with electrophysiologically guided bilateral electrolytic lesions of the PBN. The results of this experiment showed that lesions of the PBN fully prevent contrast in rats shifted from the high to the low concentration of sucrose. Thus, an intact PBN is essential for the occurrence of successive negative contrast effects in rats.

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.

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.

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.

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.

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.

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.

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.

From contrast to reinforcement: role of response contingency in anticipatory contrast.

Intake of a 0.15% saccharin solution is suppressed if access to the saccharin is followed by access to 32% sucrose in brief daily pairings. The present series of four experiments was concerned with factors that lead to this anticipatory contrast effect (suppressed saccharin intake) rather than a reinforcement effect. In Experiment 1, anticipatory contrast was obtained with an autoshaping procedure (no lick requirement on the initial tube), and degree of contrast did not vary as a function of intersolution interval in the range of 0-15 s. Experiments 2 and 3 showed that requirements of 10, 100, 200, or 400 licks on the first tube available led to a reinforcement effect in latency, but a requirement of 0 licks (autoshaping procedure) led to a contrast effect in licks and latency. In Experiment 4, a group with a 200-contingent-lick requirement showed a reinforcement effect in latency, but a group yoked to this contingent group showed a contrast effect in both latency and licks. Overall, the results suggest that anticipatory contrast occurs under conditions of a "relaxed" instrumental contingency. The data are discussed in terms of control of behavior by stimulus-stimulus, response-stimulus, and stimulus-response associations, and the results are related to behavioral contrast, to flavor-outcome associations, and to "misbehavior" produced by Pavlovian-instrumental interactions.

Relative novelty of conditioning context influences directionality of glycemic conditioning.

Previous experiments in which insulin was administered in a Pavlovian conditioning procedure obtained both hyperglycemic and hypoglycemic conditioned responses (CRs). In the present experiment the relationship of the conditioning context and the housing environment was varied. Two environments, wastebasket (WB) and metal cage (MC), were varied factorially as housing and conditioning contexts. Subgroups were injected with either insulin or saline for 6 days and then, on a test day for conditioning, all animals were administered saline. The results suggested that a hyperglycemic CR could be expected when the conditioning context is different from the housing context, but a hypoglycemic CR could be expected when the conditioning context and housing context are similar. The magnitude and reliability of conditioning were greater when it was conducted in the WB context than when conditioning was conducted in the MC context. These results are discussed in terms of stress arising from relative novelty of the conditioning environment and in terms of the salience of the conditioned stimulus (CS) used in glycemic conditioning studies.

Selective breeding for negative contrast in consummatory behavior.

Rats showing either large or small reductions in licking following a shift from 32% to 4% sucrose were selectively bred for 7 generations. Rats from the 2 resulting lines reliably differed in successive negative contrast and in activity (radial-arm maze and open field). Differences in activity and contrast were not correlated. Heritability (h2) of the reaction to sucrose shift was reliable in the last 6 filial generations and equaled 0.64 in the F7 generation. The 2 lines did not differ (a) in response to the absolute rewarding value of sucrose or cocaine; (b) in open-field defecations or thigmotaxis; (c) in anticipatory contrast; or (d) in responsivity to midazolam. Responsivity to reward reduction may involve a relatively delimited psychological process that is amenable to selection.

Investigation of the devaluation interpretation of anticipatory negative contrast.

Rats suppress intake of an acceptable substance (e.g., 0.15% saccharin) when it is followed by a preferred substance (e.g., 32% sucrose) in once per day pairings. The role of a learned devaluation of the initial solution in suppressed intake (anticipatory negative contrast) was investigated. The findings included the following: (a) Flavors or odors as within-subject cues precluded the occurrence of anticipatory contrast, conditioning flavor and odor preferences instead, which appeared to antagonize suppressed intake. (b) Anticipatory contrast was obtained when within-subject context cues, temporal alternation cues, or drinking-spout cues were used. (c) Preference tests conducted with the spout cues showed that devaluation of the initial substance was not necessary for the occurrence of negative anticipatory contrast.

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.