Role of the medial and lateral parabrachial nucleus in acquisition and retention of conditioned taste aversion in rats

Abstract

When ingestion of a taste stimulus is paired with internal malaise, the animal remembers the taste and rejects its ingestion thereafter. This learning is referred to as conditioned taste aversion (CTA). To establish CTA in adult male Wistar rats, 0.1% saccharin and an i.p. injection of 0.15 M LiCl were used as the conditioned and unconditioned stimuli, respectively. To elucidate the functional role of the medial part of the parabrachial nucleus (PBmed) which receives taste information and the lateral part (PBlat) which receives general visceral information, confined electrolytic lesions were made to either of these regions. Rats with bilateral lesions of the PBlat impaired the acquisition of CTA, but those lesions made after the acquisition of CTA had no effect on the retention of this learning. The bilateral lesions of the PBmed abolished the acquisition and retention of CTA. The PBlat-lesioned rats showed normal taste preference behavior, but PBmed-lesioned rats showed impaired sensibility to taste stimuli. These results suggest that both the PBlat and PBmed are essential for the acquisition of taste aversion learning, but the PBlat is not necessary for retrieval of CTA.

Introduction

When the consumption of novel flavored food is followed by internal malaise, animals avoid ingesting the food on subsequent presentations 4, 27, 37. It is well accepted that animals must learn to associate its taste with illness for this avoidance behavior. This type of association learning is referred to as conditioned taste aversion (CTA). Understanding of the neural mechanisms subserving the taste aversion learning has been a goal of a variety of animal experiments. In a typical experimental paradigm for CTA studies, saccharin is used as a conditioned stimulus (CS) and an intraperitoneal (i.p.) injection of lithium chloride (LiCl) is used as an unconditioned stimulus (US). In this simple model, neural information of the gustatory CS via the taste nerves is thought to be associated with that of the illness-inducing US via the visceral nerves or blood in the central nervous system. Unconditioned effects of LiCl are suggested to be mediated by the area postrema [22], and the area postrema is known to have large projections directly to the nucleus tractus solitarius (NTS) and the parabrachial nucleus (PBN) [28]. In general, both gustatory and visceral signals ascend side by side possibly by interacting with each other through the sensory relay stations and terminate in various brain areas 5, 6, 11, 25.

Although a number of lesion studies have been performed to elucidate the neural substrates of CTA (Yamamoto et al. [37]), the role of the projection zone for each of the gustatory and visceral signals in CTA formation has not been clarified because almost all the previous lesions were large enough to invade the recipient zones for the two sensory signals. The PBN is the second-order sensory relay station in the gustatory and general visceral pathways. It is generally accepted that gustatory inputs project to the medial part of the PBN (PBmed) and general visceral inputs project to the lateral part (PBlat) 12, 19. In previous lesion studies, researchers aimed to eliminate the function of the whole PBN including PBmed and PBlat, and demonstrated that the PBN was essential for the acquisition 2, 16, 21, 26, 31, 38and consolidation [17]of CTA.

One could eliminate the function of either the gustatory zone or visceral zone of the PBN with the use of a confined lesion technique. In this way, Aguero et al. [1]showed that the rats with electrolytic lesions focusing to the external lateral subnucleus in the PBlat could not acquire CTA, and interpreted this impairment of learning as the disruption of transmission of visceral malaise information. Similarly, Nader et al. [18]showed that cytotoxic lesions of the PBlat blocked the acquisition of morphine-induced CTA to saccharin, and attributed this effect to the blockade of the aversive properties of morphine in the CTA paradigm. However, no reports have examined the effects of PBlat lesions made after the conditioning procedure on the retention of CTA.

When the electrolytic lesion method was used to destroy the whole PBN in previous studies, the extents of the lesions were not always large enough to invade the entire PBN but were quite variable among the animals and depending on the researchers 7, 9, 21, 31. It is needed to correlate the lesion site in the PBN and the disruptive effects on CTA formation.

The purpose of the present study was to examine the role of the PBlat, to which illness-inducing visceral information projects, and the PBmed, to which the gustatory CS information projects, in the acquisition and retention of CTA.

Preliminary report on this work has appeared in abstract form [24].