Extinction of conditioned taste aversion depends on functional protein synthesis but not on NMDA receptor activation in the ventromedial prefrontal cortex

Abstract

We investigated the role of the ventromedial prefrontal cortex (vmPFC) in extinction of conditioned taste aversion (CTA) by microinfusing a protein synthesis inhibitor or N-methyl-d-asparate (NMDA) receptors antagonist into the vmPFC immediately following a non-reinforced extinction session. We found that the protein synthesis blocker anisomycin, but not the NMDA receptors antagonist D,L-2-amino-5-phosphonovaleric acid, impaired CTA extinction in the vmPFC. Anisomycin microinfusion into vmPFC had no effect on CTA acquisition and by itself did not induce CTA. These findings show the necessary role functional protein synthesis is playing in the vmPFC during the learning of CTA extinction.

Figure 1.

Schematic drawing of IL (infralimbic cortex) and PL (prelimbic cortex) injector tip positions (together they compose the vmPFC). Shown is a coronal view at position 3.20 and 2.70 mm anterior to bregma. Adapted with permission from Elsevier 1986, Paxinos and Watson 1986.

Figure 2.

CTA extinction learning is dependent on protein synthesis in the vmPFC. (A) Animals microinfused with anisomycin (100 μg/0.5 μL) into the vmPFC immediately following test day 1 showed marked aversion to saccharin compared with the vehicle animals throughout the experiment (*P < 0.05), except for the first test day (before drug infusion) and the last test day (day 6). Arrow denotes time of drug microinfusion. (B) Animals microinfused with anisomycin into the vmPFC immediately following the first exposure to saccharin and that received an i.p. injection of saline (instead of LiCl) were not significantly different from vehicle animals in their aversion to saccharin. (C) Animals microinfused with anisomycin into the vmPFC following exposure to saccharin on conditioning day were not significantly different from vehicle animals in their aversion to saccharin.

Figure 3.

CTA extinction learning in the vmPFC is not dependent on NMDA receptor functions. Animals microinfused with APV into the vmPFC (low dose: 2.5 μg/0.5 μL; high dose: 5 μg/0.5 μL) immediately following test day 1 were not significantly different from vehicle animals in their aversion to saccharin. Arrow denotes time of drug microinfusion.