Differential effects of thirst and satiety on conditioned taste aversion acquisition, retrieval, and memory extinction.

Thirst is an essential motivational component that could modulate the strength of conditioning; pioneer studies show that the rats' sexual dimorphism observed in the rate of aversive memory extinction of conditioned taste aversion (CTA) is affected by the state of fluid deprivation. On the other hand, previous evidence suggests that fluid intake volume and temporal context before and during conditioning may influence CTA. Furthermore, although CTA has been demonstrated using various types of stimuli, neural processing and homeostatic regulation of water and nutritional balance may differ depending on the stimulus used and the conditioning stages. Therefore, this study explored the effects of state motivated by thirst and satiation, using saccharin, as a non-caloric sweet stimulus, during CTA and the aversive memory extinction process under similar contextual and temporal conditions. First, we implemented an ad libitum water protocol in male and female adult rats to evaluate saccharin aversive memory formation; we compared this with a traditional CTA with liquid deprivation in the same context and temporal consumption conditions. Furthermore, we evaluated whether liquid satiety affects the acquisition or the aversive memory retrieval differentially. Our results show that the ad libitum liquid regimen allows reliable quantifications of basal water consumption, monitored every hour for more than five days. We observed a reliable CTA, where the magnitude of aversive memory and its extinction is significantly higher in both male and female rats; the strong CTA observed is substantially due to the satiety state during taste aversion memory retrieval. Our data show that although liquid deprivation does not affect CTA acquisition, it does induce weakness in the magnitude of aversive retrieval expression and fast aversive memory extinction, similarly in male and females. Overall, the results indicate that the need to satiate the demand for liquids during retrieval prevails over the conditioned aversion learned, suggesting, that thirst is a source of temporary variables dominating the aversive responses during CTA retrieval.

Effects of caloric or non-caloric sweetener long-term consumption on taste preferences and new aversive learning.

Food palatability and caloric content are crucial factors in guiding diet choice and amount consumed; as a result, sweet caloric tastes are associated with a positive hedonic value. Recent evidence in rodents indicates that consumption of artificial (non-caloric) sweeteners, in which sweet taste is dissociated from normal caloric consequences, could induce changes in energy and body weight regulation, suggesting that sweeteners not only modify intake and appetitive behavior, but could also change taste-learning processes. Particularly, there are different properties in some artificial sweeteners, like saccharin, that might differ from sugar in the reward responses that, after long-term consumption, could also be associated with the inability to learn new negative consequences related to the same taste. Thus, the main goal of this study was to determine, in adult rats, the effects of long-term consumption (14 days) of sugar or saccharin, on taste preference, on new aversive learning, i.e. latent inhibition (LI) of conditioned taste aversion (CTA), and appetitive taste re-learning after aversive taste associations. The results showed that 14 days' exposure to sugar, but not to saccharin, induced a significant increment in the LI of CTA and that taste preference is rapidly recovered during the next 3 days (e.g. CTA extinctions), indicating that long-term sugar consumption significantly accelerates aversive memory extinction during appetitive re-learning of a specific sweet taste; furthermore, high familiarization to sugar, but not to saccharin, promotes appetitive learning for the same taste. Overall, the results indicate that long-term consumption of sugar, but not saccharin, produces changes in appetitive re-learning and suggests that long-term sugar consumption could trigger escalating consumption due to the inability to learn new negative consequences associated with the same taste.

The role of dopamine D2 receptors in the nucleus accumbens during taste-aversive learning and memory extinction after long-term sugar consumption.

The nucleus accumbens (NAcc) is a forebrain region that may significantly contribute to the integration of taste and visceral signals during food consumption. Changes in dopamine release in the NAcc have been observed during consumption of a sweet taste and during compulsive consumption of dietary sugars, suggesting that NAcc dopaminergic transmission is strongly correlated with taste familiarity and the hedonic value content. NAcc core and shell nuclei are differentially involved during and after sugar exposure and, particularly, previous evidence suggests that dopamine D2 receptors could be related with the strength of the latent inhibition (LI) of conditioned taste aversion (CTA), which depends on the length of the taste stimulus pre-exposure. Thus, the objective of this work was to evaluate, after long-term exposure to sugar, the function of dopaminergic D2 receptors in the NAcc core during taste memory retrieval preference test, and during CTA. Adult rats were exposed during 14days to 10% sugar solution as a single liquid ad libitum. NAcc core bilateral injections of D2 dopamine receptor antagonist, haloperidol (1µg/µL), were made before third preference test and CTA acquisition. We found that sugar was similarly preferred after 3 acute presentations or 14days of continued sugar consumption and that haloperidol did not disrupt this appetitive memory retrieval. Nevertheless, D2 receptors antagonism differentially affects aversive memory formation after acute or long-term sugar consumption. These results demonstrate that NAcc dopamine D2 receptors have a differential function during CTA depending on the degree of sugar familiarity.