Lesions of the periaqueductal gray and rostral ventromedial medulla disrupt antinociceptive but not cardiovascular aversive conditional responses.

The presentation of an auditory stimulus that signals a noxious event such as foot shock results in the simultaneous expression of multiple aversive conditional responses (CRs), which include a transient elevation of arterial blood pressure (ABP) and an opioid-mediated form of hypoalgesia. Recent evidence suggests that the neural circuits responsible for the expression of these two aversive responses may overlap. In the present study, rats were trained using a Pavlovian fear conditioning paradigm in which white noise was repeatedly paired with shock. After training, groups of animals received electrolytic lesions centered in the dorsal or ventral periaqueductal gray (PAG) or in the medial or lateral rostral medulla. In sham-lesioned animals that were given paired presentations of noise and shock, subsequent presentation of the auditory stimulus caused a significant transient elevation of ABP and time-dependent inhibition of the tail flick reflex evoked by radiant heat. Lesions of either the dorsal or the ventral PAG blocked the antinociceptive CR but did not significantly affect ABP responses. Lesions of the ventromedial, but not the lateral, rostral medulla blocked hypoalgesia. Rostral medullary lesions did not reliably affect stimulus-evoked cardiovascular responses or baseline ABP. These results indicate that antinociceptive and cardiovascular conditional responses are anatomically dissociable and support our proposal that conditional hypoalgesia is mediated by a serial neural circuit that includes the amygdala, PAG, and rostral ventromedial medulla.