Re-examination of amphetamine-induced conditioned suppression of tastant intake in rats: The task-dependent drug effects hypothesis.

This study reexamined Grigson's reward comparison hypothesis (1997), which claimed to have resolved the paradox of addictive, rewarding drugs manifesting an aversive effect in the conditioned taste aversion (CTA) paradigm. Here, the authors compared the conditioned suppression effects of lithium chloride (LiCl) and amphetamine in a series of three experiments. In Experiment 1, the concentrations of saccharin solution (conditioned stimulus [CS]) and the doses of amphetamine or LiCl (unconditioned stimulus [US]) were manipulated. In Experiment 2, the effects of employing backward versus forward pairings of the CS and US were compared. Finally, in Experiment 3, the additivity of amphetamine's reward property and LiCl's aversive property was examined. The results of these experiments, respectively, indicated that: (1) manipulating saccharin solution concentrations does not distinguish the suppression effect caused by rewarding or aversive effects when amphetamine or LiCl served as the US; (2) both backward and forward pairings produced suppression of saccharin solution intake regardless of whether amphetamine or LiCl was used as the US; and (3) combining amphetamine and LiCl did not diminish the suppression effect, as would be expected if they had opposing mechanisms for the effects; instead, an additive effect occurred. Taken together, these results suggest that the drug of abuse amphetamine and the emetic drug LiCl both possess aversive properties in the CTA paradigm. No rewarding effects of amphetamine were detected in our experimental data. In all, our results do not support the Grigson's reward comparison hypothesis (1997) and a new "task-dependent drug effects hypothesis" is proposed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Temporal and Qualitative Dynamics of Conditioned Taste Aversion Processing: Combined Generalization Testing and Licking Microstructure Analysis.

The pattern of licking microstructure during various phases of a conditioned taste aversion (CTA) was evaluated. In Experiment 1, rats ingested lithium chloride (LiCl) for 3 trials and were then offered sodium chloride (NaCl) or sucrose on 3 trials. A CTA to LiCl developed and generalized to NaCl but not to sucrose. CTA intake suppression was characterized by reductions in burst size, average ingestion rate, and intraburst lick rate, and increases in brief pauses and burst counts. Compared with previous studies, LiCl licking shifted from a pattern initially matching that for normally accepted NaCl to one matching licking for normally avoided quinine hydrochloride by the end of the 1st acquisition trial. In Experiment 2, a novel paradigm was developed to show that rats expressed CTA generalization within 9 min of their first LiCl access. These results suggest that licking microstructure analysis can be used to assay changes in hedonic evaluation caused by treatments that produce aversive states. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Boosting cholinergic activity in gustatory cortex enhances the salience of a familiar conditioned stimulus in taste aversion learning.

The cholinergic system is important for learning, memory, and responses to novel stimuli. Exposure to novel, but not familiar, tastes increases extracellular acetylcholine (ACh) levels in insular cortex (IC). To further examine whether cholinergic activation is a critical signal of taste novelty, in these studies carbachol, a direct cholinergic agonist, was infused into IC before conditioned taste aversion (CTA) training with a familiar taste. By mimicking the cholinergic activation generated by novel taste exposure, it was hypothesized that a familiar taste would be treated as novel and therefore a salient target for aversion learning. As predicted, rats infused with the agonist were able to acquire CTAs to familiar saccharin. Effects of carbachol infusion on patterns of neuronal activation during conditioned stimulus–unconditioned stimulus pairing were assessed using Fos-like immunoreactivity (FLI). Familiar taste–illness pairing following carbachol, but not vehicle, induced significant elevations of FLI in amygdala, a region with reciprocal connections to IC that is also important for CTA learning. These results support the view that IC ACh activity provides a critical signal of taste novelty that facilitates CTA acquisition. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Ondansetron and Delta-9-Tetrahydrocannabinol Interfere With the Establishment of Lithium-Induced Conditioned Taste Avoidance in the House Musk Shrew (Suncus murinus).

Considerable evidence suggests that rats can learn to avoid a taste in the absence of nausea. The current experiments evaluated the potential of the antiemetic agents, ondansetron (OND) and delta-9-tetrahydrocannabinol (THC), to interfere with lithium chloride (LiCl)-induced taste avoidance in the house musk shrew, Suncus murinus, an insectivore that, unlike rats, is capable of vomiting. At a dose that did not modify saccharin (Experiment 1) or sucrose (Experiment 2) intake, OND prevented the establishment of LiCl-induced taste avoidance in the shrew. A low dose of THC (1 mg/kg), which did not modify sucrose intake during conditioning, also prevented the establishment of LiCl-induced taste avoidance in the shrew. Higher doses of THC were also effective, but they also suppressed sucrose consumption during conditioning. These results suggest that nausea is a necessary component of the unconditioned stimulus for the establishment of conditioned taste avoidance in the shrew, unlike the rat, which does not vomit when injected with a toxin. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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 (UCS), an appetitive UCS, 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 UCS (LiCl), a known reinforcing UCS (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. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Interactions between conditioned and unconditioned flavor preferences.

Five experiments investigated how rats' conditioned preferences or aversions for aqueous odors paired with sucrose or salt are affected by their unconditioned response to those tastes. Rats preferred an odor paired with 30% sucrose over an odor paired with 5% sucrose when both were presented in 5% sucrose, but they showed no preference or, if thirsty, showed the reverse preference, when the odors were presented in 30% sucrose. These changes in conditioned preference corresponded to changes in the rats' unconditioned preference for the accompanying sucrose solution. Rats' conditioned aversions for odors paired with salt showed a similar dependence on their reaction to the accompanying salt solution. The results were interpreted as showing that conditioned and unconditioned flavor preferences combine additively, as if mediated by the same sensory representation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of central and basolateral amygdala lesions on conditioned taste aversion and latent inhibition.

[Correction Notice: An erratum for this article was reported in Vol 121(6) of Behavioral Neuroscience (see record 2007-18058-034). Figure 4 on p. 96 (Results and Discussion, Experiment 2: Behavioral section) was incorrect. The correct figure is provided in the erratum.] The present study examined the effects of neurotoxic lesions of the central nucleus (CNA) and basolateral complex (BLA) of the amygdala on conditioned taste aversion (CTA) in a latent inhibition design. In Experiment 1, lesions of the CNA were found to have no affect on CTA acquisition regardless of whether the taste conditioned stimulus (CS) was novel or familiar. Lesions of the BLA, although having no influence on performance when the CS was familiar, retarded CTA acquisition when the CS was novel in Experiment 2. The pattern of results suggests that the CTA deficit in rats with BLA lesions may be a secondary consequence of a disruption of perceived stimulus novelty. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

"Effects of central and basolateral amygdala lesions on conditioned taste aversion and latent inhibition": Correction to St. Andre and Reilly (2007).

Reports an error in "Effects of Central and Basolateral Amygdala Lesions on Conditioned Taste Aversion and Latent Inhibition" by Justin St. Andre and Steve Reilly (Behavioral Neuroscience, 2007[Feb], Vol 121[1], 90-99). Figure 4 on p. 96 (Results and Discussion, Experiment 2: Behavioral section) was incorrect. The correct figure is provided in the erratum. (The following abstract of the original article appeared in record 2007-02025-008.) The present study examined the effects of neurotoxic lesions of the central nucleus (CNA) and basolateral complex (BLA) of the amygdala on conditioned taste aversion (CTA) in a latent inhibition design. In Experiment 1, lesions of the CNA were found to have no affect on CTA acquisition regardless of whether the taste conditioned stimulus (CS) was novel or familiar. Lesions of the BLA, although having no influence on performance when the CS was familiar, retarded CTA acquisition when the CS was novel in Experiment 2. The pattern of results suggests that the CTA deficit in rats with BLA lesions may be a secondary consequence of a disruption of perceived stimulus novelty. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Once is too much: Conditioned changes in accumbens dopamine following a single saccharin-morphine pairing.

The present study tested whether presentation of a taste cue would support conditioned suppression of dopamine in the nucleus accumbens (NAcc) following a single taste-drug pairing. Nondeprived male Sprague-Dawley rats were given 20-min access to a 0.15% saccharin conditioned stimulus (CS). Immediately thereafter, experimental rats were injected with morphine (15 mg/kg ip); standard controls were injected with saline; and explicitly unpaired controls were injected with morphine, but approximately 24 hr later. All rats were then given one 20-min CS-only test. Microdialysis samples from the NAcc were measured over 20-min intervals before, during, and after CS access on the conditioning and test trial. The results showed that a single saccharin-morphine pairing led to a marked reduction in CS intake, and the reduction in intake was accompanied by a conditioned blunting of the accumbens dopamine response to the saccharin reward cue. In turn, a single exposure to the saccharin cue also blunted the unconditioned dopamine response to morphine. Reward comparison effects, then, are cross-modal, bidirectional, and immediate, resulting in both unconditioned and conditioned changes in brain and behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Simultaneous backward conditioned inhibition and mediated conditioning.

Demonstrations of retrospective revaluation suggest that remembered stimuli undergo a reduction in association with the unconditioned stimulus (US) present during learning. Conversely, demonstrations of mediated conditioning in flavor-conditioning experiments with rats suggest that remembered stimuli undergo an increase in association with the US present during learning. In a food allergy prediction task with 23 undergraduates, we demonstrated simultaneous backward conditioned inhibition and mediated conditioning effects. These results are compatible with the hypothesis that the direction of change (decrease or increase) in associative strength depends on whether the remembered stimulus was of a different category (conditioned stimulus/antecedent) or the same category (US/outcome) as the presented US. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Acquired appetitive responding to intravenous nicotine reflects a Pavlovian conditioned association.

Recent research examining Pavlovian appetitive conditioning has extended the associative properties of nicotine from the unconditioned stimulus or reward to include the role of a conditional stimulus (CS), capable of acquiring the ability to evoke a conditioned response. To date, published research has used presession extravascular injections to examine nicotine as a contextual CS in that appetitive Pavlovian drug discrimination task. Two studies in the current research examined whether a nicotine CS can function discretely, multiple times within a session using passive iv infusions. In Experiment 1, rats readily acquired a discrimination in conditioned responding between nicotine and saline infusions when nicotine was selectively paired with sucrose presentations. In Experiment 2, rats were either trained with nicotine paired with sucrose or explicitly unpaired with sucrose. The results showed that rats trained with explicitly unpaired nicotine and sucrose did not increase dipper entries after the infusions. Nicotine was required to be reliably paired with sucrose for control of conditioned responding to develop. Implications of these findings are discussed in relation to tobacco addiction, learning theory, and pharmacology. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Toxin-induced conditioned changes in taste reactivity and the role of the chemosensitive area postrema

Conditioned taste avoidances (CTAs) are an important component of behavioral regulation of ingestion. In the laboratory CTAs can be produced by pairing a novel taste stimulus with the physiological feedback produced by a toxin, such as lithium. Such toxins putatively activate a chemosensitive brainstem structure, the area postrema, which ultimately results in the production of a CTA. The present review describes a series of studies which examined conditioned changes in taste reactivity responses (TRRs) when a novel intraoral sucrose taste was paired with the effects of an intraperitoneal (IP) injection of LiCl, and the role of the area postrema in the formation of conditioned palatability shifts. It was first of all necessary to examine the effects of area postrema ablations on TRRs to a range of intraoral sucrose and quinine stimulus intensities. In the first study area postrema lesioned rats exhibited concentration dependent changes in TRRs to these taste stimuli that were very similar to those exhibited by sham lesioned rats. The second study demonstrated that 30 s intraoral infusions of sucrose (0.3 M), presented at 5 or 10 min intervals following an IP injection of LiCl (3.0 meq), resulted in conditioned changes in TRRs. These were characterized by orderly, gradual reductions in ingestive responses and increases in aversive responses. Finally, when area postrema lesioned rats (Study 3) were subjected to this conditioning procedure (brief sucrose presentations paired with the effects of LiCl) no evidence for conditioned or unconditioned changes in TRRs to sucrose were obtained. Lesioned rats injected with LiCl behaved similarly to sham lesioned rats injected with NaCl. These series of studies provide evidence indicating that the chemosensitive area postrema mediates the formation of conditioned palatability shifts induced by treatment with a toxin such as lithium.     

Amphetamine's effects on food consumption and body weight: The role of adaptive processes.

Three experiments were conducted to characterize the time course of amphetamine's effects on food consumption using procedures that would allow both decreases and increases in eating to be evident relative to control levels. In Experiment 1 we measured eating over 12 postinjection hr in rats. Orderly changes in within-day temporal patterns of eating over the 12 days of amphetamine administration suggest the role of conditioned adaptive processes. In Experiment 2, animals were not presented food until 2 hr after drug administration. Initial anorexia and subsequent hyperphagia were produced by repeated administration of amphetamine. Experiment 3 assessed both within-day and over-day changes in body weight and food consumption and showed that in addition to the drug's anorectic effect, amphetamine also reduces body weight via other mechanisms. In interpreting tolerance to anorectic drugs, it is necessary to evaluate such changes in body weight that indicate shifts in hunger that occur over days as well as shifts in within-day temporal patterns of eating that indicate the presence of conditioned adaptive changes. It is proposed that these two adaptive mechanisms account for pharmacodynamic tolerance. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Latent inhibition in human affective learning.

This study presents the results of a new visual procedure designed to generate affective learning, namely the change in the affective rating of a previously. neutral stimulus by simply pairing it with a liked or disliked stimulus. Specifically, an experiment was conducted to evaluate the effect of nonreinforced preexposures to the to-be-conditioned stimulus (a non-sense shape) on affective conditioning. This manipulation, intended to produce latent inhibition, typically results in retarded learning when the preexposed stimulus is paired with the unconditioned stimulus. The results revealed that it is possible to modify the affective value of a previously neutral non-sense shape by pairing it with a liked or disliked unconditioned stimulus, and that latent inhibition affects affective conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hedonic and sensory characteristics of odors conditioned by pairing with tastants in humans.

Animals readily acquire positive odor-taste hedonic associations, but evidence for this in humans remains weak and was explored further. Retronasal pairing of odors with sucrose or salty stimuli (Experiment 1) increased the rated sweetness of sucrose-paired odors without altering liking, although changes in odor pleasantness correlated with sucrose liking. Experience of odors with sucrose or quinine by sweet likers (Experiment 2) found increased pleasantness and sweetness for sucrose-paired odors, whereas quinine-paired odors became less liked and more bitter. Odor-sucrose pairings in sweet likers and dislikers (Experiment 3) found increased sweetness in both groups but increased odor liking only in likers. These data suggest that evaluative and sensory learning are dissociable and that evaluative changes are sensitive to individual differences in sweet liking. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of prior exposure to a lithium- and an amphetamine-paired flavor on the acoustic startle response in rats.

The experiments reported here evaluated the hypothesis that an amphetamine-paired flavor elicits conditioned fear-arousal, whereas a lithium-paired flavor elicits conditioned nausea-disgust by examining the effect of prior flavor exposure on an acoustic startle reaction (ASR). Exposure to a lithium-paired flavor by intraoral infusion, either immediately prior to a startle session (Experiment 1) or during a startle session (Experiments 2 and 3), resulted in a blunted ASR. In contrast, intraoral infusion of an amphetamine-paired flavor resulted in a potentiated ASR. The blunted ASR produced by exposure to a lithium-paired flavor dramatically reversed to a potentiated ASR when rats were pretreated with the antiemetic drug ondansetron prior to the saccharin-lithium pairing (Experiment 3). The findings shed light on a mechanism by which rewarding drugs produce conditioned taste avoidance in rats. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Odor of Taste Stimuli in Conditioned "Taste" Aversion Learning.

The present research addresses whether rats can express odor aversions to the odor of taste stimuli. In Experiment 1, saccharin or salt were either mixed in distilled water, so the rats could taste and smell them, or presented on disks attached to the tubes' metal spouts so the rats could only smell them. Aversions were established to taste stimuli under both conditions. The results of Experiment 2 indicate that conditioning was to the odor of the tastes when they were presented on disks in Experiment 1, hence both taste and odor aversions were established by means of "taste" stimuli. Taste aversion learning thus may more properly be termed flavor aversion learning, with flavor referring to both taste and odor components. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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 et al, see record 84-21706) 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. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effect of the volatile oils of Chenopodium ambrosioides and Thymus vulgaris against the larvae of Lucilia sericata (Meigen)

We have isolated a stable, transplantable, and small glucagonoma (MSL-G-AN) associated with abrupt onset of severe anorexia occurring 2-3 wk after subcutaneous transplantation. Before onset of anorexia, food consumption is comparable to untreated controls. Anorexia is followed by adipsia and weight loss, and progresses rapidly in severity, eventually resulting in reduction of food and water intake of 100 and 80%, respectively. During the anorectic phase, the rats eventually become hypoglycemic and hypothermic. The tumor-associated anorexia shows no sex difference, and is not affected by bilateral abdominal vagotomy, indicating a direct central effect. The adipose satiety factor leptin, known to suppress food intake by reducing hypothalamic neuropeptide Y (NPY) levels, was not found to be expressed by the tumor, and circulating leptin levels were reduced twofold in the anorectic phase. A highly significant increase in hypothalamic (arcuate nucleus) NPY mRNA levels was found in anorectic rats compared with control animals. Since elevated hypothalamic NPY is among the most potent stimulators of feeding and a characteristic of most animal models of hyperphagia, we conclude that the MSL-G-AN glucagonoma releases circulating factor(s) that overrides the hypothalamic NPY-ergic system, thereby eliminating the orexigenic effect of NPY. We hypothesize a possible central role of proglucagon-derived peptides in the observed anorexia.     

An Extended Comparator Hypothesis Account of Superconditioning.

Three conditioned taste aversion experiments with rats investigated superconditioning. In each experiment, alternate exposures of 2 flavor compounds with a common element (i.e., AB/AS) were administered to establish an inhibitory relationship between the 2 unique elements, B and S, and prior to testing, S was paired with lithium chloride (LiCl). In Experiment 1, pairings of a neutral cue (X) with S in compound with B after the AB/AS exposures resulted in superconditioning between X and S. Extinction of the common element (A) just before the S-LiCl pairing attenuated both the inhibitory relationship between B and S (Experiment 2) and superconditioning between X and S (Experiment 3). These observations suggest that superconditioning consists of enhanced performance rather than enhanced associative acquisition. (PsycINFO Database Record (c) 2010 APA, all rights reserved)