George Wolf and Innate Mechanisms of Sodium Appetite
GEORGE WOLF. Innate mechanisms for regulation of sodium intake. In: Olfaction and Taste., edited by Carl Pfaffman. New York: Rockefeller University Press, 1969; pp 548-553.
Comments by Alan C. Spector (June, 2015)
When I was a postdoc with Harvey Grill at the University of Pennsylvania in the late 80s, I became exposed to the writings of George Wolf. Wolf had passed away a few years earlier and, sadly, I never had the opportunity to meet him, but his articles made a distinct impression on me in several ways. First, the logic was crisp. Second, the voice was objective, but with conviction. Finally, there was the rigor of strong experimental design. At the time, I was beginning to study salt taste and Harvey introduced me to a chapter by Wolf entitled Innate Mechanisms for Regulation of Salt Intake, which had been published in the proceedings of the Third International Symposium on Olfaction and Taste in 1969 (18). Harvey used the chapter for an undergraduate class he taught on the biological basis of motivated behavior, a practice which I soon adopted as well. I have chosen this chapter as an Ingestive Classic because it reflects all those positive features that characterized Wolf’s writings and importantly his thinking, and was ahead of its time by presaging a specific gustatory mechanism devoted to the detection and recognition of the sodium cation.
In this chapter, Wolf argues that sodium appetite, the enhanced ingestion of even normally avoided concentrations of sodium salts by omnivores and herbivores when deficient in the electrolyte, is: 1) innate, taste guided, and specific to the sodium cation, 2) a motivated response rather than merely a reflexive behavior, and 3) is the manifestation of neural circuits promoting the search for the specific stimulus (i.e., sodium) rather than just a process in which the reinforcing efficacy of the taste stimulus is heightened (which nonetheless occurs as well). He brings to bear three experiments conducted by his students to buttress his three conclusions.
The first is an experiment conducted by Handel (7) in which various groups of sodium-depleted rats were presented with a salt solution for the first time and licking was measured. Both a group that received an isotonic, normally preferred, concentration of NaCl and a group that received a hypertonic, normally avoided, concentration of NaCl displayed vigorous licking within seconds after sampling. Furthermore, a group that received isotonic sodium bicarbonate showed similarly enhanced licking, in contrast to the virtual absence of licking in groups that received either isotonic KCl or CaCl2. Animals that were tested non-depleted with NaCl also did not lick much. Although it is impossible to completely rule out that these animals had prior experience with the taste of NaCl, which for example is found in laboratory chow, it is safe to assume that they never tasted pure salt solutions and never in relation to repletion from sodium deficiency. Wolf argued that these results demonstrated that the depletion-induced response to sodium Is cation-specific, taste-guided, and likely innate – i.e., the depleted rats recognized the taste of sodium without requiring an opportunity to learn that ingestion of the cation leads to repletion.
In the second study discussed, Quartermain, Miller, and Wolf (14) investigated whether salt appetite met the criterion for motivated behavior advanced by Philip Teitelbaum (17), that animals would learn to perform an arbitratry response to obtain a “goal” stimulus. Quartermain et al. first pretrained rats to bar press for a water reinforcer. The rats were then subsequently depleted of sodium and prevented from any external access to the cation (e.g., they were given sodium-free chow), but now were allowed access to water. The next day, the rats were returned to the operant test chamber, where bar pressing now yielded an isotonic NaCl solution rather than water. Non-depleted animals and depleted animals that received water as the reinforcer displayed very low levels of lever pressing, whereas animals that were sodium-depleted pressed the bar at very high rates and in relation to the degree of depletion. The behavioral difference between the groups occurred within 10 min, long before the rats had ingested sufficient amounts to produce significant sodium repletion given the small amounts of the sodium reinforcer being delivered. Wolf concluded appropriately that the relationship between the depletion state and the arbitrary learned lever-pressing response, which was produced mostly in the absence of the salt stimulus contacting the taste receptors, indicates that salt appetite is a motivated behavior, not a mere reflex triggered by gustatory stimulation. This was not a trivial point given that Grill and Norgren (6) had elegantly shown that taste stimuli are capable of eliciting reflex-like tongue protrusions when delivered directly into the oral cavity (see SSIB Ingestive Classic #9) and, indeed, sodium depletion influences such taste reactivity to a hypertonic NaCl solution (2).
In the last experiment discussed, conducted by Krieckhaus and Wolf (11), Wolf convincingly contends that the behavior to obtain sodium by sodium-deficient rats does not even require the opportunity to taste the needed cation. Six groups of water-deprived rats were trained to lever-press in order to obtain water or aqueous solutions of different salts. Three of the groups received sodium salt solutions (varying by anion) as the reinforcer, one group received KCl, one received CaCl2, and one received water. After this phase, all six groups were depleted of sodium, given ad libitum access to water, and then lever-pressing was tested in extinction (meaning no reinforcer was delivered). If lever-pressing had been previously reinforced by a sodium salt, regardless of the anion, the sodium-deficient animals pressed the bar 2-3 times more than animals that had been trained with a non-sodium solution or water as the reinforcer, even though the extinction test offered no opportunity to taste sodium. Two additional groups that were trained with NaCl and water, respectively, were tested in a non-sodium-depleted state and did not press the bar any more than did the depleted animals that had been previously trained with nonsodium reinforcers. Thus, when depleted of sodium, an essential cation that cannot be substituted by any other electrolyte, rats appeared to remember how they obtained sodium in the past, even though that learning occurred under a sodium-replete state. Importantly, animals that were experimentally sodium-depleted for the first time demonstrated enhanced behavior to gain access to sodium (i.e., sodium appetite) in the complete absence of the salt, providing evidence of an innate link between the motivational state and the specific sodium taste stimulus.
In the final section of his chapter, Wolf creatively speculates on potential neural mechanisms underlying the behavior seen in these experiments. From a taste perspective, these experiments, along with findings from Nachman (12), provided convincing evidence that rats can detect the presence of sodium regardless of the anion and discriminate it from other cations, with the exception of lithium, The taste of which rats treat almost identically to that of NaCl. All of these findings led the way to the postulation of a sodium-specific taste receptor, later identified as the epithelial sodium channel (ENaC), which is expressed in a variety of sodium-absorbing tissues, and can be found in the apical membranes of a subset of taste bud cells (e.g. (3,4,8,9)). Indeed, blockade of the ENaC by the drug amiloride or genetic deletion of the channel in taste buds eliminates the depletion-induced enhancement of sodium licking in rodents, presumably because the animal can no longer recognize the cation (see (1,4,5,10,13,16)).
Behavioral work of such high caliber and rigorous thinking as displayed in Wolf’s chapter is in an alarming decline, driven by the seduction of reduction. Anthropomorphism is common, the design of behavioral experiments is often incomplete, psychological concepts are used loosely, and there is a growing predilection for authors to make over-reaching claims (but then “let he who is without sin, cast the first stone”). Nevertheless, papers such as this chapter by George Wolf (to learn more about George Wolf see (15)) stand out as a constant reminder of the way behavior can be systematically and logically interrogated, and offer a functional context in which the more elemental components of the nervous system can eventually be integrated and understood.
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10. Hill DL, Formaker BK and White KS. Perceptual characteristics of the amiloride-suppressed sodium chloride taste response in the rat. Behav Neurosci 104: 734-741, 1990.
11. Krieckhaus EE and Wolf G. Acquisition of sodium by rats: interaction of innate mechanisms and latent learning. J Comp Physiol Psychol 65: 197-201, 1968.
12. Nachman M. Taste preferences for sodium salts in adrenalectomized rats. J Comp Physiol Psychol 55: 1124-1129, 1962.
13. Ninomiya Y and Funakoshi M. Amiloride inhibition of responses of rat single chorda tympani fibers to chemical and electrical tongue stimulations. Brain Res 451: 319-325, 1988.
14. Quartermain D, Miller NE and Wolf G. Role of experience in relationship between sodium deficiency and rate of bar pressing for salt. J COMP PHYSIOL PSYCH 63: 417-420, 1967.
15. Schulkin J. Sodium Hunger: the search for a salty taste. Cambridge: Cambridge University Press, 1991.
16. Spector AC, Guagliardo NA and St.John SJ. Amiloride disrupts NaCl versus KCl discrimination performance: Implications for salt taste coding in rats. J Neurosci 16: 8115-8122, 1996.
17. Teitelbaum P. The use of operant methods in the assessment and control of motivational states. In: Operant behavior: Areas of research and application, edited by Honig WK. New York: Appleton-Century-Crofts, 1966.
18. Wolf G. Innate mechanisms for regulation of sodium intake. In: Olfaction and Taste., edited by Pfaffman C. New York: Rockefeller University Press, 1969.