D-cycloserine Enhances Short-delay, but Not Long-delay, Conditioned Taste Aversion Learning in Rats

NMDA receptors have been implicated in conditioned taste aversion (CTA), a form of associative learning with the unique temporal characteristic of associating taste and toxic stimuli across very long delays. d-cycloserine (DCS), an NMDA receptor agonist, has been shown to enhance short-delay CTA learning. Here we examined the interaction of DCS with varying temporal parameters of CTA. DCS (15 mg/kg) administered prior to the pairing of 0.125% saccharin and LiCl (38 mM, 12 ml/kg) enhanced CTA when there was a short delay between the taste-toxin pairing (10 min), but not when there was a long delay (45 min). DCS activity remained at effective levels over the long delay, because DCS administered 60 min prior to a short-delay pairing enhanced CTA. The interaction of DCS with the delay between taste stimulus onset and LiCl injection was investigated by administering DCS and then 5 min access to saccharin 45 min prior to a short-delay pairing of saccharin and LiCl. DCS failed to enhance CTA in rats pre-exposed to saccharin, even with a short delay between the second saccharin exposure and LiCl injection. These results suggest that DCS enhancement of CTA is dependent on mechanisms underlying gustatory processing during long-delay taste-toxin associations.