Differential effects of β-adrenergic receptor blockade in basolateral amygdala or insular cortex on incidental and associative taste learning

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Abstract

The importance of central β-adrenergic system has been essentially investigated in aversive/emotional learning tasks. However, recent data suggest that the β-adrenergic system is also required for incidental taste learning. In the present study we evaluated in rats whether β-adrenergic receptor activity is required for taste habituation, an incidental taste learning, and also for conditioned taste aversion (CTA) learning, an associative learning. To address this issue, a low dose of the β-adrenergic antagonist propranolol was infused before learning in either the basolateral amygdala (BLA) or the insular cortex (IC), two forebrain areas reported to play a key role in taste memory formation. Incidental taste learning was assessed using a single presentation of the sweet taste saccharin 0.1%, which is sufficient to increase saccharin consumption (relative to water baseline) during a second presentation. CTA was assessed by pairing the first saccharin 0.1% presentation with a delayed gastric malaise, thus causing a decrease in saccharin consumption (relative to water baseline) during a second presentation. Propranolol infusion in BLA (1 μg/0.2μl) or IC (2.5 μg/0.5 μl) before the first taste exposure impaired incidental taste learning but did not affect CTA. These results highlight the important role played by the β-adrenergic receptor activation in cortical and amygdaloid structures during taste learning. Moreover, they are the first to suggest that incidental learning is more sensitive to blockade of noradrenergic system than associative learning.

Introduction

Considerable evidence indicates that the noradrenergic system plays an important role in aversive and emotional memory formation in rats and humans (for reviews: Ferry et al., 1999, McGaugh, 2000). In particular, norepinephrine or noradrenergic agonists enhance, whereas noradrenergic antagonists impair, learning for many kinds of aversive learning experiences including inhibitory avoidance or contextual fear conditioning (Gallagher et al., 1977, Introini-Collison et al., 1996, Izquierdo et al., 1992, LaLumiere et al., 2003). However, recent studies indicate that disruption of noradrenergic transmission has no effect on certain aversive learning tasks such as auditory fear conditioning (Debiec and Ledoux, 2004, Lee et al., 2001, Murchinson et al., 2004), thus questioning the general role of adrenergic signaling in emotionally arousing learning.

The importance of central noradrenergic activation has also been investigated during taste learning, in particular within two forebrain structures, the insular cortex (IC) and the basolateral amygdala (BLA). These structures receive gustatory information and play a central role in taste memory formation (for reviews: Bermudez-Rattoni, 2004, Lamprecht and Dudai, 2000). Bilateral IC microinfusions of propranolol, a β-adrenergic receptor antagonist, impaired the animals’ ability to learn to avoid a taste previously paired with a visceral malaise, i.e. conditioned taste aversion (CTA), when infused before taste-malaise association (Berman, Hazvi, Neduva, & Dudai, 2000). In the same study, the effect of propranolol infusion in IC during incidental taste learning was also evaluated, using a latent inhibition paradigm. In latent inhibition, pre-exposure to a taste attenuates the effectiveness of that taste to be associated with a subsequent gastric malaise during CTA learning. β-adrenergic receptor blockade before taste pre-exposure impaired latent inhibition of CTA (without affecting perception of the taste) suggesting that IC noradrenergic activation is important for incidental as well as aversive (i.e. associative) taste learning (Berman et al., 2000). Recent data indicate that propranolol infusion into the BLA immediately after novel taste consumption had no effect on CTA (Bahar, Samuel, Hazvi, & Dudai, 2003), whereas we showed that similar treatment immediately after novel taste pre-exposure impaired latent inhibition of CTA (Miranda, LaLumiere, Buen, Bermudez-Rattoni, & McGaugh, 2003). These results suggest that noradrenergic receptor activation in BLA is necessary for incidental, but not aversive, taste learning.

These data indicate that blockade of noradrenergic system induces a similar or even stronger deficit in non aversive (incidental) compared to aversive learning. This contrasts with the general belief that noradrenergic activity is predominantly involved in aversive/emotional experiences like shock-based learning (for review see Ferry et al., 1999, McGaugh, 2000). However, some procedural details in the aforementioned studies on taste learning may contribute to these unexpected results. First, latent inhibition of CTA is not the best learning paradigm to study incidental taste learning, since this paradigm is based upon the interaction between incidental and associative/aversive memories. A task independent of any aversive components would be more appropriate to evaluate the role of noradrenergic system in incidental taste learning. Second, the absence of CTA impairment after propranolol infusion in BLA may be due to the time of drug infusion. BLA infusions were performed immediately after the novel taste consumption (Bahar et al., 2003). Since CTA impairment was obtained when IC infusions of propranolol were done before the novel taste presentation (Berman et al., 2000), the possibility that the noradrenergic transmission in BLA is required for taste processing rather than shortly after remains to be tested. Finally, BLA infusions of different propranolol doses in latent inhibition and CTA paradigms could explain the differential effect obtained in these tasks (Bahar et al., 2003, Miranda et al., 2003). All of these points require further investigation of the importance of β-adrenergic receptor activation in incidental and associative/aversive taste learning.

The present study evaluated the effects of propranolol infusions in BLA and IC in habituation taste learning and CTA. The experimental protocols for these two different kinds of learning were as close as possible in terms of stimuli, timing of treatment and doses of drug. In CTA, a single pairing of the novel sweet taste saccharin (relatively non neophobic 0.1%) with a subsequent gastric malaise induced a significant decrease of taste consumption (relative to water baseline) during a second presentation. In habituation taste learning, a single exposure to the novel taste saccharin 0.1% (without any aversive consequences) was sufficient to induce a significant increase in saccharin consumption (relative to water baseline) during a second presentation (Ferreira, Ferry, Ravel, & Lévy, 2005a; V. De la Cruz, F. Bermudez-Rattoni and G. Ferreira, in preparation). Similar drug doses (5 μg/μl) and time of treatment (before novel taste presentation) were used for each learning task and for each brain structure investigated.

Section snippets

Subjects

Ninety five male Wistar rats (Instituto de Neurobiologı´a breeding colony, Mexico; 250–300 g at time of surgery) were used. They were housed individually at 23 °C and maintained under a 12 h light–dark cycle (lights off from 9:00 a.m. to 9:00 p.m.). Training and testing occurred in the home-cage between 10:00 a.m. and 2:00 p.m., i.e. during the dark portion of the cycle. Food and water were available ad libitum until the beginning of the behavioral procedures. Experiments were performed in México

Experiment 1: Effects of propranolol infusion in BLA on incidental taste learning

Animals were habituated to drink water twice a day during 15 min for 6 days (see Section 2). During the last 3 days of water baseline (day 4–6), there was no statistical difference between groups in the mean water intake during the first (one-way ANOVA, F(2, 27) = 1.8, p > 0.1; mean water intake when all groups were pooled: 15.2 ± 0.3 ml) and second daily presentations (F(2, 27) = 1.7, p > 0.1; 6.3 ± 0.2 ml).

On day 7, saline (0.2 μl/side) or propranolol (1 μg /0.2 μl) infusions in BLA were performed 5 min before

Discussion

The current findings indicate that local infusions of a low dose of the β-adrenergic antagonist propranolol in BLA or IC prevented incidental taste learning but did not affect associative/aversive taste learning.

Previous studies showed that β-adrenergic receptor blockade in IC before taste pre-exposure, or immediately after taste pre-exposure in the BLA, impaired latent inhibition of CTA (Berman et al., 2000, Miranda et al., 2003). However, since latent inhibition is based upon the interaction

Acknowledgments

We thank Martı´n Garcı´a for the animal maintenance, Cipriana Bravo and Mireya Romero for technical assistance, and Shaun Harris for the English revision of the final text. This work was supported by PAPIIT IN201308, CONACyT C54524, 46161 M, 46754 Q (M.I.M.) and by ANR-05-PNRA-002 (G.F.).

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