Rapid, Labile, and Protein Synthesis– Independent Short-Term Memory in Conditioned Taste Aversion

Conditioned taste aversion (CTA) is a form of associative learning in which an animal avoids the taste of a food previously paired with toxic effects. CTA has a number of unique temporal properties that distinguish it from other forms of learning and memory. Unlike most other forms of learning, CTA learning is single-trial, long-delay, and persistent. Rather than requiring multiple acquisition trials, a robust CTA can be acquired after a single pairing (Garcia and Koelling 1967). CTA can be acquired even when the contingent presentations of taste and toxin are separated by extremely long intervals (up to 12 hr; Garcia et al. 1966; Smith and Roll 1967). CTA learning appears to be optimized for long delays, because simultaneous or short-delay pairing is less effective than long-delay pairing (Schafe et al. 1995). CTAs are also extremely persistent, with little or no loss of memory months after a small number of trials (Houpt et al. 1996). These adaptations of CTA learning to a lengthy time course have been correlated with the need to associate the acute taste of a poisonous food with toxic events that may be life threatening, but occur hours after ingestion (Garcia and Ervin 1968). Because the prolonged nature of CTA learning distinguishes it from other forms of learning, most research has focused on the long time course of CTA memory (days to months after pairing taste and toxin). There have been few studies of CTA memory in the short-term (minutes to hours after pairing). The existence of short-term memory in other forms of learning is well established, but a short-term memory phase has never been demonstrated formally in CTA learning. If a learned behavior has a short-term memory phase, it must meet at least three criteria: 1) it should be acquired rapidly and expressed within minutes; 2) it should be labile and forgotten rapidly within minutes to hours under some conditions; and 3) it should be expressed in the absence of protein synthesis prior to long-term consolidation. In this study we demonstrate that CTA learning in rats has a short-term memory phase that meets these three criteria. We employed a CTA paradigm in which a palatable, sweet taste (5% sucrose) was paired with toxic injections of lithium chloride 30 min after presentation of the taste solution (Houpt et al. 1994). Because we used this paradigm, the short-term time course of CTA expression was tested under conditions that (1) support long-delay learning; (2) mediate long-term taste aversions (e.g., up to 6 months after three pairings; Houpt et al. 1996); and (3) use intake as the behavioral measure of CTA expression. Rats were outfitted with chronic intraoral catheters. Intraoral infusions of the taste stimulus were employed because this allows a standard orosensory stimulus to be presented to all rats regardless of deprivation state or somatic behavioral response. This makes the test of CTA expression more analogous to other learning paradigms, in which a standard stimulus is presented both before and after conditioning (e.g., the tone paired with shock in fear conditioning). Intraoral infusions have proven to be a very sensitive measure of CTA expression that parallels the independent ingestive responses measured by ad lib bottle intake (Grill and Berridge 1985). In ad lib bottle tests, however, the rat is not presented with a standard and controlled stimulus, because presentation of the stimulus from the bottle is confounded by competing somatic behaviors. For example, expression of the transient “lying-on-belly” behavior induced by acute LiCl injection is incompatible with ad lib drinking from a bottle. Intraoral infusions avoid this confound: Rats can consume (or reject) an intraoral infusion even when expressing competing behaviors such as rearing, grooming, etc. Rats were infused intraorally with 5% sucrose at arbitrary times after pairing with LiCl. Intake was measured by weighing the rats immediately before and after the intraoral infusions. The expression of the CTA was followed over time by giving the rats a standard intraoral infusion of sucrose between 15 min and 48 hrs after pairing. CTA acquisition was found to be rapid, because a CTA was expressed within 15 min. In addition, the dose of LiCl paired with intraoral infusions of sucrose was varied to determine if the short-term expression and long-term consolidation of a CTA could be dissociated. In fact, CTA memory was found to be labile at lower doses of LiCl, but long lasting at the highest dose employed. Finally, administration of the protein synthesis inhibitor cycloheximide between the intraoral infusion of sucrose and the injection of LiCl did not attenuate short-term CTA expression but blocked long-term CTA expression completely. Thus, the short-term expression of a CTA is also protein synthesis independent.