Specific inter-stimulus interval effect of NMDA receptor activation in the insular cortex during conditioned taste aversion.

Taste memory recognition is crucial for species survival; thus, the acquisition of conditioned taste aversion (CTA) protects animals against consuming poisons or toxins. In nature, food and poison are confined in the same edible item; however, in the laboratory these food constituents are usually presented separately for experimental analysis. The taste, or conditioned stimulus (CS), can be hours apart from the gastric malaise, or unconditioned stimulus (US); this extended inter-stimulus interval (ISI) allows the analysis of a particular learning phase. Evidence indicates a relevant function of glutamatergic activity in the insular cortex (IC) throughout the ISI. N-methyl-D-aspartate receptors (NMDAR) are crucial during CTA acquisition and retrieval. However, the exact participation of NMDAR in the IC during the ISI has not been demonstrated. Thus, the aim of this work was to evaluate the effects of temporal NMDAR activation during four time frames throughout the ISI of conditioned sugar aversion with bilateral injections of NMDA at a physiological dose (1 µg/µl) in the IC, given (1) immediately before or (2) immediately after sugar presentation, or (3) immediately before or (4) immediately after LiCl i.p. injection. The results showed that NMDAR activation in the IC had a specific ISI effect during CTA acquisition, increasing aversive memory formation and delaying extinction only after CS presentation. Overall, these results demonstrate that NMDAR in the IC have a particular enhancing associative effect after CS and suggest that there is a precise coincidence in neurochemical events in the IC that correlates with the stimulus to be associated and the glutamate NMDAR activity that must be finely tuned in the ISI during CTA acquisition.