Administration of riluzole to the basolateral amygdala facilitates fear extinction in rats

Abstract A general understanding exists that inhibition of glutamatergic neurotransmission in the basolateral amygdala (BLA) impairs fear extinction in rodents. Surprisingly, we recently found that systemic administration of riluzole, which has been shown to inhibit the glutamatergic system, facilitates extinction learning in rats with a preconditioned contextual fear response. However, the mechanisms underlying this paradoxical effect of riluzole remain unclear. In this study, adult male Wistar rats were bilaterally cannulated in the BLA to examine the effects of intra-BLA administration of riluzole. We also compared the effects of riluzole with those of d -cycloserine, a partial agonist at the glycine-binding region of the N -methyl- d -aspartate (NMDA) receptor. In this study, intra-BLA administration of either riluzole or d -cycloserine facilitated extinction learning of contextual fear in conditioned rats. In addition, both riluzole and d -cycloserine enhanced the acquisition of recognition memory in the same model. However, intra-BLA injections of riluzole, but not d -cycloserine, had a potent anxiolytic-like effect when investigated using an elevated plus-maze test. Our findings suggest that riluzole-induced facilitation of extinction learning in rats with a preconditioned contextual fear reflects an indirect effect, resulting from the intra-BLA administration of the drug, and might not be directly related to inhibition of glutamatergic signaling. Further research is needed to clarify the mechanisms underlying the paradoxical effect of riluzole on fear extinction learning observed in this study.