Classic CTA papers
This is a set of CTA papers that illustrate the key properties of taste aversion learning -- either the first demonstration of
I have also written an overview of critical issues in CTA learning.
1. Historical Origins of CTA Learning
2. Basic Properties of CTA Learning
3. Anatomical Pathways for CTA learning
4. Examples of Toxins and Other Unconditioned Stimuli
1. Historical Origins of CTA Learning
frog paper
bait shyness
Papers from the Kimeldorf Lab
Garcia, J., D.J. Kimeldorf,and R.A. Koelling. Conditioned aversion to saccharin resulting from exposure to gamma radiation. Science (1955) 157-158. [PDF]
Garcia, J., D.J. Kimeldorf, E.L. Hunt, and B.P. Davies. Food and water consumption of rats during exposure to gamma radiation. Radiation Res. 4 (1956) 33-41. [PDF]
Garcia, J. and D.J. Kimeldorf, and E.L. Hunt. Conditioned responses to manipulative procedures resulting from exposure to gamma radiation. Radiation Res. 5 (1956) 79-87. [PDF]
Garcia, J. and D.J. Kimeldorf. Temporal relationship within the conditioning of a saccharine aversion through radiation exposure. J. Comp. Physiol. Psychol. 50 (1957) 180-183. [PDF]
Garcia, J. and D.J. Kimeldorf. The effect of ophthalmectomy upon responses of the rat to radiation and taste stimuli. J. Comp. Physiol. Psychol. 51 (1958) 288-291. [PDF]
Garcia, J. and D.J. Kimeldorf. Conditioned avoidance behavior induced by low-dose neutron exposure. Nature 185 (1960) 261-262. [PDF]
Kimeldorf, D.J., J. Garcia, and D. O. Rubadeau. Radiation-induced conditioned avoidance behavior in rats, mice, and cats. Radiation Res. 12 (1960) 710-718. [PDF]
Garcia, J. and D.J. Kimeldorf. Some factors which influence radiation-conditioned behavior of rats. Radiation Res. 12 (1960) 719-727. [PDF]
2. Basic Properties of CTA Learning
Single Pairing
Garcia? something that parameterized it?
Long delay CTA learning tolerates a very long delay between taste and toxin (up to hours), unlike other forms of associative conditioning that toletate only seconds between CS and US.
Garcia, J., F. R. Ervin, and R.A. Koelling. Learning with prolonged delay of reinforcement, Psychonomic Sci. 5 (1966) 121-122. [PDF]
Smith, J.C. and D.L. Roll, Trace conditioning with X-rays as an aversive stimulus. Psychon. Sci., 9 (1967) 11.
Revusky SH, Bedarf EW. Association of illness with prior ingestion of novel foods.
Science. 155 (1967) 219-20. [PDF]Schafe, G.E., S.I. Sollars, and I.L. Bernstein, The CS-US interval and taste aversion learning: a brief look. Behav. Neurosci. 109 (1995.) 799-802. CTA learning may actually be optimized for long delay learning.
Persistent
Forgetting:
Houpt, T.A., J.M. Philopena, T.H. Joh and G.P. Smith. c-Fos induction in the rat nucleus of the solitary tract correlates with the retention and forgetting of a conditioned taste aversion. Learning & Memory 3 (1996) 25-30. PMID: 10456073 [PDF]
Extinction:
Spector, A.C., J.C. Smith, and G.R. Hollander. A comparison of dependent measures used to quantify radiation-induced taste aversion. Physiol. Behav. 27 (1981) 887-901. [PDF] A thorough comparison of the rates of extinction in 2-bottle preference tests after CTAs acquired to different doses of radiation. We refer to this paper all the time in our lab meeting, because Alan showed that different groups of rats extinguish at different rates -- a few rats in every experiment never extinguish at all.
Houpt, T.A., J. M. Philopena, T. C. Wessel, T. H. Joh and G. P. Smith. Altered c-fos expression in the rat nucleus of the solitary tract following conditioned taste aversion formation. Neurosci. Lett. 172 (1994) 1-5. PMID: 8084508 [PDF]
Preparedness for taste and toxin association. Taste and flavor CSs are best associated with internal malaise-inducing CSs (i.e. enteroceptive stimuli) while visual and auditory CSs are best associated with shock (i.e. exteroceptive stimuli).
Garcia, J. and R.A. Koelling. Relation of cue to consequence in avoidance learning. Psychonomic Sci. 4(1966) 123-124. [PDF] The bright and noisy water experiment.
Odor Potentiation Odor potentiates condition taste aversion learning.
Palmerino, C.C., K.W. Rusiniak, and J. Garcia. Flavor-illness aversions: the peculiar roles of odor and taste in memory for poison. Science, 208 (1980) 753-755 [PDF]
Short-term and Long-term memory CTA has a protein synthesis-independent. short-term memory phase and a protein synthesis dependent long-term memory phase.
Houpt, T.A. and R.A. Berlin. Rapid, labile and protein-synthesis-independent short-term memory in conditioned taste aversion. Learning & Memory 6 (1999) 37-46. PMID: 10355522 [PDF]
CREB antisense
Novelty vs. Learned Safety
Kalat, J. W. and P. Rozin. "Learned Safety" as a mechanism in long-delay taste-aversion learning in rats. J. Comp. Physiol. Psychol. 83 (198-207) [PDF]
Hedonic Shift from Ingestive to Aversive responses
Grill, H.J. and R. Norgren. The taste reactivity test. I. Mimetic responses to gustatory stimuli in neurologically normal rats. Brain Res. 143 (1978) 263-279. [PDF]
Grill, H.J. Physiological mechanisms in conditioned taste aversions., Ann NY Acad. Sci. 443 (1985) 67-88. [PDF]
Breslin, P.A.S., A.C. Spector, and H.J. Grill. A quantitative comparison of taste reactivity behaviors to sucrose before and after lithium chloride pairings: a unidimensional account of palatability. Behav. Neurosci. 106 (1992) 820-836. [PDF]
Taste Specificity
Nowlis, G.H., M.E. Frank, and C. Pfaffmann. Specificity of acquired aversions to taste qualities in hamsters and rats, J. Comp. Physiol. Psychol. 94 (1980) 932-942. [PDF]
Taste Aversions in Humans
Bernstein IL. Learned taste aversions in children receiving chemotherapy. Science. 200 (1978) 1302-3.
Smith JC, Blumsack JT, Bilek FS, Spector AC, Hollander GR, Baker DL. Radiation-induced taste aversion as a factor in cancer therapy. Cancer Treat Rep. 68 (1984) 1219-27.
3. Anatomical Pathways for CTA learning
We also have a useful powerpoint slide summarizing the neural circuitry underlying CTA learning.
vagal vs humoral pathways coil & norgren
Area postrema Bernstein, Ritter
decerebration Grill and Norgren
GLP-1 and caudal NTS Seeley?
rostral NTS (not much effect) Spector?
pbn lesion Spector, Norgren
thalamus (not much effect) Spector?
amygdala (basolateral, central)
gustatory cortex
hypothalamus ?
4. Examples of CTA Unconditioned Stimuli
Almost any treatment seems capable of acting as the US in CTA acquisition. Listed here are some key papers describing some common or emblematic stimuli. There are some discrete categories: historically-used toxins (lithium, radiation); physiologically relevant toxins (LPS , copper sulfate, amino acid deficient diets); non-pharmacological vestibular treatments (rotation, optokinesis, and magnetic fields); durgs of abuse (morphine, amphetamine) and orexigenic treatments (NPY, 2DG) that paradoxically induce CTA.
I have included at the end of the list a paper by Ervin comparing the ability of compounds to induce satiety or induce CTA; the two functions appear independent, such that satiety factors (e.g. CCK) are good at decreasing feeding but poor at inducing CTA, while toxins (e.g. lithium) are good at CTA but not very good at acutely decreasing food intake.
Lithium: Nachman, M. and J.H. Ashe. Learned taste aversions in rats as a function of dosage, concentration, and route of administration of LiCl. Physiol. Behav. 10 (1973) 73-78.
Radiation: Garcia, J., D.J. Kimeldorf,and R.A. Koelling. Conditioned aversion to saccharin resulting from exposure to gamma radiation. Science (1955) 157-158. [PDF]
Lipopolysaccharide (bacterial cell-wall component):
Copper Sulfate (intravenous vs. intragastric): Coil JD, Norgren R. Taste aversions conditioned with intravenous copper sulfate: attenuation by ablation of the area postrema. Brain Res. 212(1981):425-33. Detection of i.v. CuSO4 requires the area postrema, but detection of intragastric CUSO4 (acting as a gastric irritant) does not. There is also an interesting unconditioned response to CuS04 in the rumen of the newborn calf, by which the irritant causes rapid stomach emptying via the reticular groove. (see the Merck Veterinary Manual)
Amino acid deficient diets:
Glucagon-Like Peptide-1: Thiele TE, Van Dijk G, Campfield LA, Smith FJ, Burn P, Woods SC, Bernstein IL, Seeley RJ. Central infusion of GLP-1, but not leptin, produces conditioned taste aversions in rats. Am J Physiol. 272 (1997) R726-30.
Rotation:
Optokinesis:
Magnetic Field Exposure: Nolte, C.M., D.W. Pittman, B. Kalevitch, R. Henderson, and J.C. Smith. Magnetic field conditioned taste aversion in rats. Physiol. Behav. 63 (1998) 683-688. [PDF] See also the our webpage on magnetic field effects.
Morphine (drug of abuse):
Amphetamine (drug of abuse):
Neuropeptide Y (orexigenic after central injection): Sipols AJ, Brief DJ, Ginter KL, Saghafi S, Woods SC. Neuropeptide Y paradoxically increases food intake yet causes conditioned flavor aversions. Physiol Behav. 51 (1992) 1257-60.
2-Deoxyglucose (orexigenic after peripheral injection): Stephan FK, Smith JC, Fisher E. Profound conditioned taste aversion induced by oral consumption of 2-deoxy-D-glucose. Physiol Behav. 68 (1999) 221-6.
Anorectic Potency vs. CTA-mediation: Ervin GN, Birkemo LS, Johnson MF, Conger LK, Mosher JT, Menius JA Jr. The effects of anorectic and aversive agents on deprivation-induced feeding and taste aversion conditioning in rats. J Pharmacol Exp Ther. 273 (1995) 1203-10. [PDF]