Swim-stress but not opioid withdrawal increases expression of c-fos immunoreactivity in rat periaqueductal gray neurons which project to the rostral ventromedial medulla

Abstract

Expression of c-fos-like immunoreactivity has been used as a marker for neuronal activation and is elevated in the periaqueductal gray following stressful and noxious stimuli, and opioid withdrawal. The present study examined the staining of c-fos-like immunoreactivity following opiate withdrawal or swim-stress (2.5-3 min at 21 degrees C) in periaqueductal gray neurons of the rat which had projections to and through the rostral ventromedial medulla identified by microinjection of the retrograde tracer, Fast Blue, into the nucleus raphe magnus prior to development of morphine dependence. Both naloxone-precipitated withdrawal and swim-stress increased numbers of neurons expressing c-fos-like immunoreactivity in periaqueductal gray. Naloxone-precipitated withdrawal did not increase the number of double-labelled neurons in periaqueductal gray suggesting that neurons excited during opioid withdrawal do not project to the ventromedial medulla. In contrast, swim-stress produced increases in double-labelled neurons in periaqueductal gray suggesting that many periaqueductal gray neurons activated by swim-stress project to the ventromedial medulla. These findings suggest that naloxone-precipitated withdrawal does not activate ventrolateral periaqueductal gray neurons which are involved in descending inhibitory pathways, consistent with behavioural observations that naloxone-precipitated withdrawal is qualitatively opposite to electrical and chemical stimulation of the ventrolateral periaqueductal gray. The results are also consistent with a role of descending projections from periaqueductal gray in stress-induced antinociception.