Modulation of Conditioned Fear, Fear-Conditioned Analgesia, and Brain Regional C-Fos Expression Following Administration of Muscimol into the Rat Basolateral Amygdala

Evidence suggests that gamma-aminobutyric acid (GABA) signalling in the basolateral amygdala (BLA) is involved in pain, fear, and fear-conditioned analgesia (FCA). In this study, we investigated the effects of intra-BLA administration of the GABA(A) receptor agonist muscimol on the expression of conditioned-fear, formalin-evoked nociception, and fear-conditioned analgesia in rats, and the associated alterations in brain regional expression of the immediate early gene product and marker of neuronal activity, c-Fos. Formalin-evoked nociceptive behavior, conditioned-fear and fear-conditioned analgesia were apparent in animals receiving intra-BLA saline. Intra-BLA muscimol suppressed fear behavior and prevented fear-conditioned analgesia, but had no significant effect on the expression of formalin-evoked nociception. The suppression of fear behavior by intra-BLA muscimol was associated with increased c-Fos expression in the central nucleus of the amygdala (CeA) and throughout the periaqueductal grey (PAG). These intra-BLA muscimol-induced increases in c-Fos expression were abolished in rats receiving intraplantar formalin injection. These data suggest that alterations in neuronal activity in the CeA and PAG as a result of altered GABAergic signalling in the BLA may be involved in the behavioral expression of fear and associated analgesia. Furthermore, these alterations in neuronal activity are susceptible to modulation by formalin-evoked nociceptive input in a state-dependent manner. Perspective: The expression of learned fear and associated analgesia are under the control of GABA(A) receptors in the basolateral amygdala, through a mechanism which may involve altered neuronal activity in key components of the descending inhibitory pain pathway. The results enhance our understanding of the neural mechanisms subserving fear-pain interactions. (C) 2011 by the American Pain Society