OPIOID INHIBITION OF RAT PERIAQUEDUCTAL GREY NEURONS WITH IDENTIFIED PROJECTIONS TO ROSTRAL VENTROMEDIAL MEDULLA IN-VITRO

1. Rat caudal periaqueductal grey (PAG) output neurones containing rho damine microspheres, retrogradely transported from an injection site i n the rostral ventromedial medulla (RVM), were visualized in brain sli ces and recorded from using whole-cell patch clamp techniques. 2. The specific GABA(B) receptor agonist baclofen (10 mu M) produced an outwa rd current or hyperpolarization in fifty out of fifty-six caudal PAG o utput neurones. In 44% of these baclofen-sensitive neurones, the opioi d agonist methionine enkephalin (30 mu M) also produced an outward cur rent or hyperpolarization. The opioid current reversed polarity at -10 4 mV and could also be produced by DAMGO, an agonist selective for the mu-subtype of opioid receptor. 3. Opioid-responding output neurones w ere not distributed uniformly in the caudal PAG. In horizontal slices containing lateral PAG, 56 % of output neurones were inhibited by opio ids, as compared with only 14 % of the output neurones in slices conta ining ventrolateral PAG. 4. These observations are consistent with opi oid disinhibition of ventrolateral PAG neurones projecting to the RVM as the predominant mechanism underlying opioid-induced analgesia in th e PAG. The role of opioid receptors found on a major proportion of the output neurones in the lateral PAG remains to be established, but is assumed not to be related to modulation of nociceptive function.