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.

Chemical stimulation or glutamate injections in the nucleus of solitary tract enhance conditioned taste aversion.

Taste memory depends on motivational and post-ingestional consequences after a single taste-illness pairing. During conditioned taste aversion (CTA), the taste and visceral pathways reach the nucleus of the solitary tract (NTS), which is the first relay in the CNS and has a vital function in receiving vagal chemical stimuli and humoral signals from the area postrema that receives peripheral inputs also via vagal afferent fibers. The specific aim of the present set of experiments was to determine if the NTS is involved in the noradrenergic and glutamatergic activation of the basolateral amygdala (BLA) during CTA. Using in vivo microdialysis, we examined whether chemical NTS stimulation induces norepinephrine (NE) and/or glutamate changes in the BLA during visceral stimulation with intraperitoneal (i.p.) injections of low (0.08 M) and high (0.3 M) concentrations of lithium chloride (LiCl) during CTA training. The results showed that strength of CTA can be elicited by chemical NTS stimulation (Ringer's high potassium solution; 110 mM KCl) and by intra-NTS microinjections of glutamate, immediately after, but not before, low LiCl i.p. injections that only induce a week aversive memory. However visceral stimulation (with low or high i.p. LiCl) did not induce significantly more NE release in the amygdala compared with the NE increment induced by NTS potassium depolarization. In contrast, high i.p. concentrations of LiCl and chemical NTS stimulation induced a modest glutamate sustained release, that it is not observed with low LiCl i.p. injections. These results indicate that the NTS mainly mediates the visceral stimulus processing by sustained releasing glutamate in the BLA, but not by directly modulating NE release in the BLA during CTA acquisition, providing new evidence that the NTS has an important function in the transmission of signals from the periphery to brain systems that process aversive memory formation.

Nucleus of the solitary tract chemical stimulation induces extracellular norepinephrine release in the lateral and basolateral amygdala.

The NTS catecholaminergic neurons, activated by a variety of afferent stimuli, are ideally situated to coordinate afferent signaling to multiple brain regions. In particular, there is evidence that systemic epinephrine injections induce a significant increase of norepinephrine (NE) in the amygdala during enhanced memory, which can be disrupted by NTS chemical blockade or interruption of vagal afferents. The present experiment was conducted to obtain information about the levels of NE release induced by activation of the whole NTS, which projects to the lateral and basolateral amygdala. Therefore, we compared NE levels before and after general stimulation of the NTS and the amygdala in anesthetized rats, without any behavioral or vagal stimulation, to find out the degree of noradrenergic activation modulated by the NTS through all its projections to the lateral and basolateral amygdala, as well as the degree of noradrenergic activation which may occur locally in the amygdala through rapid and general activation of this structure.