A Pharmacological Perspective of Drugs Used in Establishing Conditioned Food Aversions<sup>a</sup>

Gamzu, Elkan; Vincent, George P.; Boff, Edward

doi:10.1111/j.1749-6632.1985.tb27077.x

Cited by 67 publications

(28 citation statements)

References 103 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Still, the possibility exists that the effects seen after taste-LiCl pairing are due to some unique properties of LiCl. We have therefore replaced LiCl with another malaise-inducing agent, CuS04 (27). CTA obtained with this US was similar to that obtained in the routine CTA training procedure using LiCl (the conditioned rats preferred water to saccharin at a ratio of 9:1 in a multiple choice test).…”

Section: Resultsmentioning

confidence: 64%

“…The effect of the US may involve convergence of signal transduction cascade(s) activated by the sensation of malaise on the signal transduction cascade(s) modulated by the taste input, thus resulting in augmentation of the cellular effect of taste alone in the insular cortex to a level that markedly modulates protein tyrosine phosphorylation. In this context it is pertinent to note that LiCl and CuSO4 may act in vivo via different anatomical pathways (27), and yet the effect on protein tyrosine phosphorylation in cortex is apparently similar. required for normal learning of the novel taste (14,28), but association of the taste with malaise can take place in the absence of normal cortical activity (28).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Modulation of protein tyrosine phosphorylation in rat insular cortex after conditioned taste aversion training.

Rosenblum

Schul

Meiri

et al. 1995

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Protein tyrosine phosphorylation is a major signal transduction pathway involved in cellular metabolism, growth, and differentiation. Recent data indicate that tyrosine phosphorylation also plays a role in neuronal plasticity. We are using conditioned taste aversion, a fast and robust associative learning paradigm subserved among other brain areas by the insular cortex, to investigate molecular correlates of learning and memory in the rat cortex. In conditioned taste aversion, rats learn to associate a novel taste (e.g., saccharin) with delayed poisoning (e.g., by LiCl injection). Here we report that after conditioned taste aversion training, there is a rapid and marked increase in tyrosine phosphorylation of a set of proteins in the insular cortex but not in other brain areas. A major protein so modulated, of 180 kDa, is abundant in a membrane fraction and remains modulated for more than an hour after training. Exposure of the rats to the novel taste alone results in only a small modulation of the aforementioned proteins whereas administration of the malaise-inducing agent per se has no effect. To the best of our knowledge, this is the first demonstration of modulation of protein tyrosine phosphorylation in the brain after a behavioral experience.Protein tyrosine phosphorylation is a major signal transduction pathway involved in cellular metabolism, growth, and differentiation (1). Recently, it became apparent that tyrosine phosphorylation also plays a key function in neuronal activity and plasticity. Activation of receptor tyrosine kinases by growth and neurotrophic factors is required for development, remodeling, and possibly also maintenance of neural tissue. Prominent among this class of molecules are members of the trk family that respond to a variety of neurotrophic factors including nerve growth factor, brain-derived neurotrophic factor, and neurotrophin 3 (2-4). Protein tyrosine kinases appear also to be involved in mediating the effect of neural cell adhesion molecules on neuronal membrane-associated cytoskeleton (5) and in modulating neurotransmitter receptors (6, 7). In addition, activation of nonreceptor protein tyrosine kinases may play a role in encoding intracellular neuronal responses to specific ligands, probably in the context of cross-talk between signal transduction cascades (8-10).The function of protein tyrosine phosphorylation in longterm structural modification of neurons is especially pertinent to the study of behavioral plasticity, since consolidation of long-term memory is postulated to involve modulation of gene expression, culminating in altered synaptic morphology and physiology (11,12). Indeed, inhibitors of protein tyrosine kinase were reported to block long-term potentiation in hippocampal CAl region in the guinea pig (9) and knockout of the fyn gene, encoding a nonreceptor tyrosine kinase, was found to impair long-term potentiation, spatial learning, and hippocampal morphology in transgenic mice (13).Analysis of the modulation of protein tyrosine phosphorylation in brai...

show abstract

Section: Resultsmentioning

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Modulation of protein tyrosine phosphorylation in rat insular cortex after conditioned taste aversion training.

Rosenblum

Schul

Meiri

et al. 1995

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…These treatments were known to activate emetic mechanisms NUTRITIONAL ASPECTS OF RECOVERY F R O M SEVERE ILLNESS and it appeared that food aversion learning was a response to symptoms of internal malaise, especially nausea. Since that time, however, there have been hundreds of studies employing dozens of different pharmacological agents and it is clear that many agents which are capable of producing learned food aversions do not produce aversive emetic symptoms (Gamzu et al 1985). It is generally agreed, then, that nausea is not a necessary condition for the development of learned food aversions.…”

Section: Nature Of the Unconditioned Stimulusmentioning

confidence: 99%

Development of food aversions during illness

Bernstein

1994

Proc. Nutr. Soc.

View full text Add to dashboard Cite

Food aversions, particularly those which are acquired as a result of unpleasant experiences with foods, represent a potent defence mechanism against poisoning. Humans, as well as a broad range of animal species, appear strongly predisposed to associate certain symptoms of discomfort with foods they have eaten and to subsequently dislike and avoid those foods. Although food aversion learning serves a clearly adaptive function in certain circumstances, there appear to be other situations, such as chronic illness, in which food aversions arise and have deleterious effects on nutritional status and general health. The present article will review the basic research literature on food aversion learning and then go on to a discussion of evidence that chronic illness can be associated with the development of food aversions, and that such aversions can affect food intake and body weight. Although many of these studies were done in rats, evidence for comparable processes in humans will be included when available. FOOD AVERSION LEARNING

show abstract

“…CFA is a sensitive assay, such that a CFA can be observed in the absence of any other apparent toxic effect (Gamzu et al 1985). The formation of a robust CFA often requires only one conditioning trial (Garcia and Kimeldorf 1957).…”

mentioning

confidence: 99%

Systemic 5-bromo-2-deoxyuridine induces conditioned flavor aversion and c-Fos in the visceral neuraxis

Kimbrough¹,

Kwon²,

Eckel³

et al. 2011

Learn. Mem.

View full text Add to dashboard Cite

5-bromo-2-deoxyuridine (BrdU) is often used in studies of adult neurogenesis and olfactory learning, but it can also have toxic effects on highly proliferative tissue. We found that pairing Kool-Aid flavors with acute systemic injections of BrdU induced strong conditioned flavor aversions. Intermittent injections during Kool-Aid-glucose conditioning interfered with learning of a conditioned flavor-nutrient preference. Acute injection of BrdU also elevated plasma corticosterone levels and induced c-Fos in the visceral neuraxis. Thus, acute or intermittent systemic injections of BrdU (50-200 mg/kg) have aversive effects that may interfere with learning.5-bromo-2-deoxyuridine (BrdU), a thymidine analog, incorporates into daughter DNA during the S-phase of cell division, marking new cells. BrdU is commonly used to label proliferation of new neurons in the mammalian brain during adult neurogenesis that may contribute to learning. Enhanced hippocampal neurogenesis, as labeled by BrdU, improves long-term spatial and visual recognition memory (Thuret et al. 2009). Additionally, olfactory learning impacts survival of newborn neurons (labeled with BrdU) after integration in the adult olfactory bulb (Mouret et al. 2008).BrdU is often used in adult neurogenesis associative learning paradigms such as olfactory discrimination (as measured by habituation/disinhibition or by olfactory-cued reward task) (Mandairon et al. 2006;Mouret et al. 2008Mouret et al. , 2009 A potential confound for studies of adult neurogenesis in learning and memory is the toxicity of BrdU. Systemic injections of BrdU could have aversive consequences that might alter or influence learning. Because BrdU is incorporated into rapidly dividing cells, it can be toxic to highly proliferative tissues. BrdU has well-known teratogenic effects (Franz and Kleinebrecht 1982;Kolb et al. 1999). It also has been used for cancer treatment based on toxicity to and radiosensitization of mitotically active tumor cells (Lawrence et al. 1992).BrdU is toxic to normal tissues with high proliferation rates, such as the skin and gastrointestinal tract. For example, in clinical trials of systemic BrdU in humans, BrdU caused rashes, mucositis, nail loss, and exfoliative dermatitis (Levin et al. 1995). BrdU is incorporated heavily in the intestine as early as 1 h following i.p. injection (Kriss and Revesz 1962), suggesting possible effects on endothelial proliferation within the lining of the gut. High doses of chronic BrdU (e.g., 200 mg/kg/day for 10 d) led to weight loss in mice (Lawrence et al. 1992).BrdU is toxic to proliferating neurons at high doses in vitro (Caldwell et al. 2005). However, doses of 100-600 mg/kg i.p. have been found to be nontoxic to proliferating neurons in the hippocampus of adult rats (Cameron and McKay 2001). Nonetheless, BrdU might have aversive effects secondary to toxic effects on proliferative tissues in the periphery, such as in the gastrointestinal tract.To determine whether BrdU has toxic effects that would impact behavior and neural processing, w...

show abstract

A Pharmacological Perspective of Drugs Used in Establishing Conditioned Food Aversions^a

Cited by 67 publications

References 103 publications

Modulation of protein tyrosine phosphorylation in rat insular cortex after conditioned taste aversion training.

Modulation of protein tyrosine phosphorylation in rat insular cortex after conditioned taste aversion training.

Development of food aversions during illness

Systemic 5-bromo-2-deoxyuridine induces conditioned flavor aversion and c-Fos in the visceral neuraxis

Contact Info

Product

Resources

About

A Pharmacological Perspective of Drugs Used in Establishing Conditioned Food Aversionsa

Cited by 67 publications

References 103 publications

Modulation of protein tyrosine phosphorylation in rat insular cortex after conditioned taste aversion training.

Modulation of protein tyrosine phosphorylation in rat insular cortex after conditioned taste aversion training.

Development of food aversions during illness

Systemic 5-bromo-2-deoxyuridine induces conditioned flavor aversion and c-Fos in the visceral neuraxis

Contact Info

Product

Resources

About

A Pharmacological Perspective of Drugs Used in Establishing Conditioned Food Aversions^a