Joe Arthurs

Conditioned taste aversion, drugs of abuse and palatability.

We consider conditioned taste aversion to involve a learned reduction in the palatability of a taste (and hence in amount consumed) based on the association that develops when a taste experience is followed by gastrointestinal malaise. The present article evaluates the well-established finding that drugs of abuse, at doses that are otherwise considered rewarding and self-administered, cause intake suppression. Our recent work using lick pattern analysis shows that drugs of abuse also cause a palatability downshift and, therefore, support conditioned taste aversion learning.

Reduced palatability in drug-induced taste aversion: II. Aversive and rewarding unconditioned stimuli.

Drugs of abuse are known to reduce intake of a taste conditioned stimulus (conditional stimulus, CS), a behavioral response sometimes seen as paradoxical because the same drugs also serve as rewards in other behavioral procedures. In the present study we compared patterns of intake and palatability (assessed using microstructural analysis of licking) for a standard saccharin CS paired with the following: lithium chloride, morphine, amphetamine, or sucrose. We found that morphine and amphetamine, like lithium-induced illness, each suppressed CS intake and caused a reduction in saccharin palatability. Sucrose, a rewarding stimulus, did not reduce the palatability of the saccharin CS. We interpret these finds as evidence that drugs of abuse induce conditioned taste aversions.

Reduced Palatability in Drug-Induced Taste Aversion: I. Variations in the Initial Value of the Conditioned Stimulus

Like illness-inducing agents (e.g., lithium chloride), drugs of abuse also suppress intake of a taste solution. To explore the nature of this drug-induced intake reduction, in the current study three aqueous stimuli with different initial values served as the conditioned stimuli (CSs) that were paired with a standard dose of amphetamine in a voluntary intake procedure and lick patterns were analyzed. Consistent with earlier studies, amphetamine significantly reduced intake of all three CSs (quinine, sodium chloride, and orange odor). In contrast to studies that analyze orofacial responses, we found that lick cluster size was significantly lowered by amphetamine, indicating that the psychoactive drug induced a conditioned reduction in taste palatability.

Taste neophobia and c-Fos expression in the rat brain.

Taste neophobia refers to a reduction in consumption of a novel taste relative to when it is familiar. To gain more understanding of the neural basis of this phenomenon, the current study examined whether a novel taste (0.5% saccharin) supports a different pattern of c-Fos expression than the same taste when it is familiar. Results revealed that the taste of the novel saccharin solution evoked more Fos immunoreactivity than the familiar taste of saccharin in the basolateral region of the amygdala, central nucleus of the amygdala, gustatory portion of the thalamus, and the gustatory insular cortex. No such differential expression was found in the other examined areas, including the bed nucleus of stria terminalis,medial amygdala, and medial parabrachial nucleus. The present results are discussed with respect to a forebrain taste neophobia system.

Conditioned taste aversions: From poisons to pain to drugs of abuse

Learning what to eat and what not to eat is fundamental to our well-being, quality of life, and survival. In particular, the acquisition of conditioned taste aversions (CTAs) protects all animals (including humans) against ingesting foods that contain poisons or toxins. Counterintuitively, CTAs can also develop in situations in which we know with absolute certainty that the food did not cause the subsequent aversive systemic effect. Recent nonhuman animal research, analyzing palatability shifts, has indicated that a wider range of stimuli than has been traditionally acknowledged can induce CTAs. This article integrates these new findings with a reappraisal of some known characteristics of CTA and presents a novel conceptual analysis that is broader and more comprehensive than previous accounts of CTA learning.

Reduced palatability in pain-induced conditioned taste aversions

The current study investigated whether internal pain-inducing agents can modulate palatability of a tastant in the same way as illness-inducing agents (e.g., lithium chloride). Similar to traditional conditioned taste aversion (CTA) experiments, during conditioning the rats were exposed to a saccharin solution followed by intraperitoneal injections of either gallamine (Experiment 1) or hypertonic sodium chloride (NaCl; Experiments 1 and 2). In addition to the total amount consumed, the time of each lick was recorded for lick pattern analysis. The results showed that both gallamine and hypertonic NaCl caused suppression in saccharin intake. Importantly, both lick cluster size and initial lick rate (the measures of taste palatability) were reduced as well. This pattern of results suggests that these pain-inducing agents reduce the hedonic value of the associated tastant and thus CTA is acquired. The current finding serves as evidence supporting the view that CTA is a broadly tuned mechanism that can be triggered by changes in internal body states following consummatory experience.

Role of the Gustatory Thalamus in Taste Learning

The present study re-examined the involvement of the gustatory thalamus (GT) in the acquisition of drug- and toxin-induced conditioned taste aversions (CTAs) using a standardized procedure involving 15-min taste trials in rats injected with morphine (Experiment 1), lithium chloride (Experiment 2) or amphetamine (Experiment 3). Contrary to previous results, GT lesions did not eliminate drug-induced CTAs. Rather, GT-lesioned rats acquired aversions of comparable magnitude to non-lesioned subjects but from an elevated intake on the first conditioning trial. A similar pattern of lesion effects was found in the acquisition of an illness-induced CTA. Thus, we conclude that GT lesions do not differentially influence CTAs conditioned with drugs or toxins. The lesion-induced elevated intake of a novel tastant confirms an unappreciated role for the GT in taste neophobia.

Gustatory insular cortex, aversive taste memory and taste neophobia

Prior research indicates a role for the gustatory insular cortex (GC) in taste neophobia. Rats with lesions of the GC show much weaker avoidance to a novel and potentially dangerous taste than do neurologically intact animals. The current study used the retention of conditioned taste aversion (CTA) as a tool to determine whether the GC modulates neophobia by processing taste novelty or taste danger. The results show that GC lesions attenuate CTA retention (Experiment 1) and impair taste neophobia (Experiment 2). Given that normal CTA retention does not involve the processing of taste novelty, the pattern of results suggests that the GC is involved in taste neophobia via its function in processing the danger conveyed by a taste stimulus.

Role of the insular cortex in morphine-induced conditioned taste avoidance.

The present study investigated the role of the insular cortex (IC) in morphine-induced conditioned taste avoidance. The results of Experiment 1 revealed that IC lesions impaired taste neophobia, retarded acquisition of conditioned saccharin avoidance and apparently attenuated the magnitude of that response at asymptote. Using neurologically intact subjects, Experiment 2 established that a safe and familiar saccharin stimulus supports substantially weaker conditioned avoidance at asymptote than does a potentially dangerous and novel saccharin stimulus. This pattern of results does not support the hypothesis that IC lesions disrupt the learning mechanism responsible for morphine-induced conditioned taste avoidance. The data are, however, consistent with the hypothesis that IC lesions impair the perception of the danger and/or novelty of the taste stimulus.

Anisomycin infusions in the parabrachial nucleus and taste neophobia.

To investigate whether de novo protein synthesis in the parabrachial nucleus (PBN) is required for recovery from taste neophobia, anisomycin (a protein synthesis inhibitor) was infused immediately after consumption of a novel saccharin solution (Experiment 1). Unexpectedly, this PBN treatment caused a reduction in saccharin intake. In addition, we found that the anisomycin-induced suppression of tastant intake was attenuated by prior intra-PBN infusions of lidocaine (Experiment 2). This pattern of results raises concerns about using anisomycin to investigate memory consolidation processes in the PBN. Thus, a different manipulation may be needed to examine the nature of the neuroplastic changes that occur in the PBN during taste memory formation.