Temporal and Qualitative Dynamics of Conditioned Taste Aversion Processing: Combined Generalization Testing and Licking Microstructure Analysis.

The pattern of licking microstructure during various phases of a conditioned taste aversion (CTA) was evaluated. In Experiment 1, rats ingested lithium chloride (LiCl) for 3 trials and were then offered sodium chloride (NaCl) or sucrose on 3 trials. A CTA to LiCl developed and generalized to NaCl but not to sucrose. CTA intake suppression was characterized by reductions in burst size, average ingestion rate, and intraburst lick rate, and increases in brief pauses and burst counts. Compared with previous studies, LiCl licking shifted from a pattern initially matching that for normally accepted NaCl to one matching licking for normally avoided quinine hydrochloride by the end of the 1st acquisition trial. In Experiment 2, a novel paradigm was developed to show that rats expressed CTA generalization within 9 min of their first LiCl access. These results suggest that licking microstructure analysis can be used to assay changes in hedonic evaluation caused by treatments that produce aversive states. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The parabrachial nucleus: A brain stem substrate critical for mediating the aversive motivational effects of morphine.

Bilateral ibotenic acid lesions of the lateral, but not the medial, parabrachial nucleus (PBN) blocked conditioned taste aversion (CTA) induced by morphine but not conditioned place preference induced by morphine. The same lateral PBN lesions also blocked conditioned place aversion produced by low intraperitoneal doses of morphine (shown to produce aversion, instead of preference, due to a restricted action on gut opiate receptors). Lateral PBN lesions did not block CTA produced by LiCl. Cerebral peduncle lesions that destroyed the direct descending projections from the visceral cortex to the PBN did not block CTA induced by morphine, nor did ibotenic acid lesions of the tegmental pedunculopontine nuclei (shown to block place preference produced by even high morphine doses). It is suggested that the lateral PBN is a critical link in the neural pathway carrying the aversive motivational effects of opiates from the gut into the CNS, independent of the neural pathway carrying the rewarding motivational effects of morphine. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Boosting cholinergic activity in gustatory cortex enhances the salience of a familiar conditioned stimulus in taste aversion learning.

The cholinergic system is important for learning, memory, and responses to novel stimuli. Exposure to novel, but not familiar, tastes increases extracellular acetylcholine (ACh) levels in insular cortex (IC). To further examine whether cholinergic activation is a critical signal of taste novelty, in these studies carbachol, a direct cholinergic agonist, was infused into IC before conditioned taste aversion (CTA) training with a familiar taste. By mimicking the cholinergic activation generated by novel taste exposure, it was hypothesized that a familiar taste would be treated as novel and therefore a salient target for aversion learning. As predicted, rats infused with the agonist were able to acquire CTAs to familiar saccharin. Effects of carbachol infusion on patterns of neuronal activation during conditioned stimulus–unconditioned stimulus pairing were assessed using Fos-like immunoreactivity (FLI). Familiar taste–illness pairing following carbachol, but not vehicle, induced significant elevations of FLI in amygdala, a region with reciprocal connections to IC that is also important for CTA learning. These results support the view that IC ACh activity provides a critical signal of taste novelty that facilitates CTA acquisition. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Rationale for en bloc vein resection in the treatment of pancreatic adenocarcinoma adherent to the superior mesenteric-portal vein confluence. Pancreatic Tumor Study Group

The enzymatic activity of protein kinase C (PKC) was measured in the cytosol and particulate fraction of parabrachial nucleus, the presumed site of conditioned taste aversion (CTA) engrams. At various time intervals after acquisition of the task (pairing saccharin consumption with subsequent LiCl poisoning) the nucleus was dissected from the frozen coronal sections. An increase (+40%) in the cytosol PKC activity was found 48 h after that pairing in comparison with controls (saline injection instead of LiCl). Particulate enzyme activity virtual did not change (-5%). Thus the total PKC activity increased significantly (21%). Qualitatively similar but less markedly expressed PKC shifts (+18% in cytosol) ere found 24 h following CTA. Twelve hours and 5 days after CTA acquisition the activity and distribution of PKC was similar to that seen in normal rats. The control experiments revealed that 6 h after LiCl injection alone (without previous saccharin consumption) translocation of PKC from the cytosol to the membrane fraction (found previously 1 h after LiCl injection alone) still persisted but did not differ from that found 6 h after its pairing with saccharin drinking (CTA). It is concluded that acquisition of conditioned taste aversion may be followed by synthesis of PKC rather than by its translocation or downregulation.     

Attenuation of ethanol-induced conditioned taste aversion in mice sensitized to the locomotor stimulant effects of ethanol.

This study examined the effect of repeated ethanol (EtOH) injections that induced behavioral sensitization on subsequent acquisition of EtOH- and lithium chloride (LiCl)-induced conditioned taste aversion (CTA). CTA acquisition was assessed in independent groups of EtOH-sensitized and nonsensitized genetically heterogeneous female mice after injections of saline; 1, 2, or 4 g/kg EtOH; or 2 or 4 mEq/kg LiCl. Saline and 1 g/kg EtOH did not induce CTA. Four g/kg EtOH and 4 mEq/kg LiCl induced similar levels of CTA in EtOH-sensitized and nonsensitized groups. CTA induced by 2 g/kg EtOH and 2 mEq/kg LiCl was attenuated in EtOH-sensitized mice compared with nonsensitized counterparts. Thus, a sensitizing regimen of EtOH preexposure resulted in both a decrease in EtOH and LiCl aversion and an increase in EtOH locomotor sensitivity; such changes could ultimately contribute to enhanced EtOH intake and potentially to EtOH abuse. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of lesions of the bed nucleus of the stria terminalis, lateral hypothalamus, or insular cortex on conditioned taste aversion and conditioned odor aversion.

The effects of permanent forebrain lesions on conditioned taste aversions (CTAs) and conditioned odor aversions (COAs) were examined in 3 experiments. In Experiment 1, lesions of the bed nucleus of the stria terminalis had no influence on CTA or COA acquisition. Although lesions of the lateral hypothalamus induced severe hypodipsia in Experiment 2, they did not prevent the acquisition of CTAs or COAs. Finally, in Experiment 3, lesions of the insular cortex retarded CTA acquisition but had no influence on COA acquisition. The implications of these findings are discussed with regard to the forebrain influence on parabrachial nucleus function during CTA acquisition. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Role of the perirhinal cortex in rats' conditioned taste aversion response memorization.

The role of the perirhinal cortex (PC) in conditioned taste aversion (CTA) learning was investigated in Long-Evans rats. CTA was induced by the intraperitoneal administration of LiCl 60 min after saccharin-sweetened water drinking. The PC was reversibly inactivated by the stereotaxic administration of tetrodotoxin (TTX) 60 min before saccharin drinking, immediately after saccharin drinking (Experiment 1), 6 or 24 hr after LiCl administration (Experiment 2), and 60 min before CTA retrieval testing (Experiment 3). Only pre-saccharin drinking PC inactivation disrupted CTA. Thus, PC integrity is necessary only during the earliest phases of CTA mnemonic processing, that is, taste information acquisition and early gustatory memory elaboration. The results are discussed in relation to PC connectivity and PC temporal involvement in the memorization process of other aversive responses. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cycloheximide impairs reconsolidation of a contextually reactivated memory in a conditioned taste aversion paradigm.

Rats were used to examine the impact of systemic protein synthesis inhibition (PSI) on the reconsolidation of a contextually reactivated memory of conditioned taste aversion (CTA). Rats were administered intraperitoneal injections of saline or lithium chloride (LiCl; .15 M) following exposure to a novel sucrose solution in a unique context. Seven days later, rats were injected subcutaneously with saline or cycloheximide (CXM; 1 mg/kg) and returned to their home cage or placed into the CTA training context in the absence of the target conditioned stimulus to reactivate the training memory. At testing, LiCl-trained rats that had been given CXM at reactivation had significantly greater difference scores (sucrose-water) in comparison with LiCl/CXM rats that had not been given a reactivation treatment and LiCl/saline memory-reactivated rats. These results suggest that context re-exposure effectively reactivates memory of CTA training that may be weakened through PSI. Extinction tests revealed rapid attenuation of taste aversions in all of the LiCl-injected groups. The involvement of taste-potentiated aversions and the role of the context in taste aversion conditioning are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of central and basolateral amygdala lesions on conditioned taste aversion and latent inhibition.

[Correction Notice: An erratum for this article was reported in Vol 121(6) of Behavioral Neuroscience (see record 2007-18058-034). Figure 4 on p. 96 (Results and Discussion, Experiment 2: Behavioral section) was incorrect. The correct figure is provided in the erratum.] The present study examined the effects of neurotoxic lesions of the central nucleus (CNA) and basolateral complex (BLA) of the amygdala on conditioned taste aversion (CTA) in a latent inhibition design. In Experiment 1, lesions of the CNA were found to have no affect on CTA acquisition regardless of whether the taste conditioned stimulus (CS) was novel or familiar. Lesions of the BLA, although having no influence on performance when the CS was familiar, retarded CTA acquisition when the CS was novel in Experiment 2. The pattern of results suggests that the CTA deficit in rats with BLA lesions may be a secondary consequence of a disruption of perceived stimulus novelty. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

"Effects of central and basolateral amygdala lesions on conditioned taste aversion and latent inhibition": Correction to St. Andre and Reilly (2007).

Reports an error in "Effects of Central and Basolateral Amygdala Lesions on Conditioned Taste Aversion and Latent Inhibition" by Justin St. Andre and Steve Reilly (Behavioral Neuroscience, 2007[Feb], Vol 121[1], 90-99). Figure 4 on p. 96 (Results and Discussion, Experiment 2: Behavioral section) was incorrect. The correct figure is provided in the erratum. (The following abstract of the original article appeared in record 2007-02025-008.) The present study examined the effects of neurotoxic lesions of the central nucleus (CNA) and basolateral complex (BLA) of the amygdala on conditioned taste aversion (CTA) in a latent inhibition design. In Experiment 1, lesions of the CNA were found to have no affect on CTA acquisition regardless of whether the taste conditioned stimulus (CS) was novel or familiar. Lesions of the BLA, although having no influence on performance when the CS was familiar, retarded CTA acquisition when the CS was novel in Experiment 2. The pattern of results suggests that the CTA deficit in rats with BLA lesions may be a secondary consequence of a disruption of perceived stimulus novelty. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Parabrachial nucleus lesions block taste and attenuate flavor preference and aversion conditioning in rats.

Rats with ibotenic acid lesions of the parabrachial nucleus (PBN) failed to learn a taste aversion induced by lithium chloride (LiCl) toxicosis. The same rats also did not learn to prefer a taste that was paired with intragastric (IG) carbohydrate infusions during 22 hr/day trials. The PBN-lesioned rats did learn to prefer a flavor (odor?+?taste) paired with the IG carbohydrate infusions over a different flavor paired with IG water. The PBN-lesioned rats also learned to avoid a flavor paired with IG LiCl infusions during 22 hr/day trials. The flavor preference and aversion, however, were less pronounced than those displayed by control rats. These data indicate that the PBN is essential for forming orosensory-viscerosensory associations when taste is the primary cue but is less critical when more complex flavor cues are available. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Comparison of formation of D2/E2-isoprostanes and F2-isoprostanes in vitro and in vivo--effects of oxygen tension and glutathione

Rats with extensive ibotenic acid lesions centered in the gustatory zone of the pontine parabrachial nucleus (PBN) failed to acquire a conditioned taste aversion (CTA) induced by lithium chloride (LiCl) toxicosis (Experiments 1 and 4). This deficit cannot be explained as an inability to either perceive or process gustatory information because lesioned rats that failed to acquire a CTA readily acquired a conditioned flavor preference (Experiment 2). Similarly, the CTA deficit cannot be attributed to an inability to experience or process visceral input because PBN-lesioned rats that failed to acquire a CTA successfully learned an aversion to a trigeminal stimulus, capsaicin, when paired with LiCl-induced illness (Experiment 3). This pattern of results supports the view that cell bodies within the PBN are essential for the associative processes that govern CTA learning.     

Ibotenic acid lesions of the parabrachial nucleus and conditioned taste aversion: Further evidence for an associative deficit in rats.

Rats with extensive ibotenic acid lesions centered in the gustatory zone of the pontine parabrachial nucleus (PBN) failed to acquire a conditioned taste aversion (CTA) induced by lithium chloride (LiCl) toxicosis (Experiments 1 and 4). This deficit cannot be explained as an inability to either perceive or process gustatory information because lesioned rats that failed to acquire a CTA readily acquired a conditioned flavor preference (Experiment 2). Similarly, the CTA deficit cannot be attributed to an inability to experience or process visceral input because PBN-lesioned rats that failed to acquire a CTA successfully learned an aversion to a trigeminal stimulus, capsaicin, when paired with LiCl-induced illness (Experiment 3). This pattern of results supports the view that cell bodies within the PBN are essential for the associative processes that govern CTA learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Involvement of the supramammillary nucleus in aversive conditioning.

Mechanisms for the retention and retrieval of conditioned taste aversions (CTAs) have yet to be fully defined. The authors explored relevant subcortical forebrain regions by tracking the expression of immediate early genes, c-fos and zif268. The supramammillary nucleus (SuM) was activated following both viscerally based CTA and somatically based inhibitory avoidance (IA). Excitotoxic lesions of the SuM before conditioning caused no disruption of acquisition but accelerated the extinction of both the CTA and IA. In contrast, lesions after CTA conditioning did not impair retention or retrieval. The present study indicates that the SuM is activated by memory-elicited discomfort during retrieval, suggesting that it plays a role in resisting the extinction of a long-term aversive memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of hypothermia on the acquisition of conditioned taste aversion in rats.

Analyzed the mechanism of conditioned taste aversion (CTA) by subjecting 131 male and hooded rats in 5 experiments to reduced body temperature during various phases of CTA acquisition. A 15-min access to .1% saccharin served as the CS, and an ip injection of LiCl (.15 M, 4% of body weight) given 30 min later served as the UCS. Hypothermia (cooling to 20-22°C colonic temperature) alone or combined with anesthesia (Nembutal 20 or 40 mg/kg) did not prevent CTA acquisition when applied during the CS-UCS interval. Hypothermia induced immediately after LiCl administration to anesthetized or unanesthetized Ss failed to disrupt CTA or to increase neophobic rejection of saccharin. On the other hand, hypothermic Ss were not able to form the short-term gustatory trace when the CS (2% saccharin, 1% of body weight) was injected ip, although this procedure yielded significant CTA in euthermic Ss. It is concluded that the most vulnerable link of CTA acquisition is the formation of the short-term gustatory trace. Persistence of the short-term trace, its association with poisoning, and consolidation of the permanent CTA engram are accomplished by mechanisms that are resistant to hypothermia and/or anesthesia. (39 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Parabrachial gustatory lesions impair taste aversion learning in rats.

Lesions in the gustatory zone of the parabrachial nuclei (PBN) severely impair acquisition of a conditioned taste aversion (CTA) in rats. To test whether this deficit has a memorial basis, 15 intact rats and 10 rats with PBN lesions (PBNX) received 7 intraoral taste stimulus infusions (30 sec, 0.5 ml) distributed over a 30.5-min period after either LiCl or NaCl injection. This task measures the rapid formation of a CTA and has minimum demands on memory. LiCl-injected intact rats progressively changed their oromotor response profiles from one of ingestion to one of aversion. NaCl-injected intact rats did not change their ingestive pattern of responding. In contrast, there was no difference between LiCl- and NaCl-injected PBNX rats. These same PBNX rats failed to avoid licking the taste stimulus when tested in a different paradigm. A simple impairment in a memorial process is not likely the basis for the CTA deficit. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The NMDA receptor antagonist CPP impairs conditioned taste aversion and insular cortex long-term potentiation in vivo

It has been proposed that long-term potentiation (LTP) a form of activity-dependent modification of synaptic efficacy, may be a synaptic mechanism for certain types of learning. Recent studies on the insular cortex (IC) a region of the temporal cortex implicated in the acquisition and storage of conditioned taste aversion (CTA), have demonstrated that tetanic stimulation of the basolateral nucleus of the amygdala (Bla) induce an N-methyl-d-aspartate (NMDA) dependent LTP in the IC of adult rats in vivo. Here we present experimental data showing that intracortical administration of the NMDA receptor competitive antagonist CPP (-3(-2 carboxipiperazin-4-yl)-propyl-1-phosphonic acid) disrupts the acquisition of conditioned taste aversion, as well as, the IC-LTP induction in vivo. These findings are of particular interest since they provide support for the view that the neural mechanisms underlying NMDA dependent neocortical LTP, constitute a possible mechanism for the learning related functions performed by the IC.     

Conditioned taste aversion is disrupted by prolonged retrograde effects of intracerebral injection of tetrodotoxin in rats.

Acquisition of conditioned taste aversion (CTA) is disrupted when 10 ng tetrodotoxin (TTX) is injected into both parabrachial nuclei of rats immediately after saccharin drinking and before LiCl poisoning (S. F. Ivanova & J. Bure?, in press). Further analysis of this finding showed that parabrachial TTX injection (1) elicited retrograde amnesia also when applied 1, 2, or 4 days but not 8 days after CTA acquisition; (2) did not abolish CTA produced by 2 or 3 saccharin–LiCl pairings; (3) did not cause persistent increase of quinine threshold; and (4) elicited anterograde CTA amnesia when applied 1 but not 2, 4, or 8 days before CTA acquisition. TTX-induced amnesia is not due to persistent gustatory agnosia but rather to disruption of the protracted consolidation of the permanent CTA engram by prolonged cessation of impulse activity in the information storing network. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Polycose taste pre-exposure fails to influence behavioral and neural indices of taste novelty.

Taste novelty can strongly modulate the speed and efficacy of taste aversion learning. Novel sweet tastes enhance c-Fos-like immunoreactivity (FLI) in the central amygdala and insular cortex. The present studies examined whether this neural correlate of novelty extends to different taste types by measuring FLI signals after exposure to novel and familiar polysaccharide (Polycose?) and salt (NaCl) tastes. Novel Polycose not only failed to elevate FLI expression in central amygdala and insular cortex, but also failed to induce stronger taste aversion learning than familiar Polycose. Novel NaCl, on the other hand, showed patterns of FLI activation and aversion learning similar to that of novel sweet tastes. Possible reasons for the resistance of Polycose to typical pre-exposure effects are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)