Alterations in Extracellular Levels of Gamma-Aminobutyric Acid in the Rat Basolateral Amygdala and Periaqueductal Gray During Conditioned Fear, Persistent Pain and Fear-Conditioned Analgesia

Evidence suggests an important role for supraspinal gamma-aminobutyric acid (GABA) in conditioned fear and pain. Using dual probe microdialysis coupled to HPLC, we investigated alterations in extracellular levels of GABA simultaneously in the rat basolateral amygdala and dorsal periaqueductal gray during expression of conditioned fear, formalin-evoked nociception, and fear-conditioned analgesia. Re-exposure to a context previously paired with footshock significantly increased the duration of freezing and 22-kilohertz ultrasonic vocalization, and reduced formalin-evoked nociceptive behavior. Upon re-exposure to the context, GABA levels in the basolateral amygdala were significantly lower in fear-conditioned animals compared with non-fear-conditioned controls, irrespective of intraplantar formalin/saline injection. GABA levels in the dorsal periaqueductal gray were lower in rats receiving intraplantar injection of formalin, compared with saline-treated controls. GABA levels sampled were sensitive to nipecotic acid and calcium infusion. No specific fear-conditioned analgesia-related alterations in GABA efflux were observed in these regions despite the ability of rats undergoing dual probe microdialysis to express this important survival response. In conclusion, expression of contextually induced fear- and pain-related behavior are accompanied by suppression of GABA release in the basolateral amygdala and dorsal periaqueductal gray, respectively, compared with non-fear, non-pain controls. Perspective: This study investigates alterations in levels of the neurotransmitter GABA simultaneously in the rat amygdala and periaqueductal grey during expression of pain- and fear-related behavior and fear-induced analgesia. The results enhance our understanding of the role of this neurotransmitter in pain, memory of pain and control of pain during fear.