Spontaneous recovery of a conditioned taste aversion differentially alters extinction-induced changes in c-Fos protein expression in rat amygdala and neocortex

Abstract

Conditioned taste aversions (CTAs) may be acquired when an animal consumes a novel taste (conditioned stimulus; CS) and then experiences the symptoms of poisoning (unconditioned stimulus; US). Animals will later avoid the taste that was previously associated with malaise. Extinction of a CTA is observed following repeated, non-reinforced exposures to the CS and represents itself as a resumption of eating/drinking the once-avoided tastant. Spontaneous recovery (SR) of a CTA (a revival of the taste avoidance) occurs when the CS is offered after a latency period in which the CS was not presented. An initial study explored the experimental parameters required to produce a reliable SR following acquisition and extinction of a robust CTA in rats. A CTA was formed through 3 pairings of 0.3% oral saccharin (SAC) and 81 mg/kg i.p. lithium chloride (LiCl) followed by extinction training resulting in 90% reacceptance of SAC. After extinction training, some of the animals were also tested for SR of the CTA upon exposure to SAC following a 15-, 30-, or 60-day latency period of water drinking. We report here that latencies of 15, 30, or 60 days produced small, but reliable, SRs of the CTA—with longer latencies producing progressively more suppression of SAC consumption. A second study investigated changes in the amygdala (AMY), gustatory neocortex (GNC), and medial prefrontal cortex (mPFC) functioning during SR of a CTA. Using immunohistochemical methods, brain c-Fos protein expression was analyzed in rats that extinguished the CTA as well as those that exhibited SR of the CTA after a 30-day latency. Our previous studies indicated that the numbers of c-Fos-labeled neurons in GNC and mPFC is low following CTA acquisition and increase dramatically as rats fully extinguished the aversion. Here we report that cortical c-Fos protein expression declines significantly following SR of the CTA. Expression of c-Fos in basolateral AMY decreased significantly from EXT to SR, but control animals with an intact CTA also decreased significantly from a short-term CTA test to a long-term CTA test. Low levels of c-Fos expression in the central nucleus of the amygdala (CE) were observed throughout EXT with little change in expression detectable following SR. These measurements reflect the dynamic nature of brain activity during acquisition and extinction of a CTA and highlight an important role for cortical neurons in the brain reorganization that occurs during SR of a CTA. The data also suggest that certain sub-nuclei of the AMY may play a relatively minor role in SR of this defensive reaction to a learned fear.