INVOLVEMENT OF ALPHA-2-RECEPTORS IN THE ANALGESIA INDUCED BY TRANSIENT FOREBRAIN ISCHEMIA IN RATS

Transient forebrain ischemia induced in rats by the four-vessel occlus ion method produced analgesic effects in the hotplate test that persis ted for 2 weeks. Ischemia-induced analgesia was attenuated by low dose s of alpha2-agonist clonidine (0.01-0.10 mg/kg, IP) and enhanced by lo w doses of alpha2-antagonists yohimbine (1-2 mg/kg, IP) and idazoxan ( 0.25-1.00 mg/kg, IP) administration 7 days after ischemia. Ischemia-in duced analgesia was not affected by methysergide, naloxone, propranolo l, or phenoxybenzamine administered 7 days after ischemia, when motor control and arousal level of rats recovered to normal conditions. The enhanced response to yohimbine was antagonized by pretreatment with cl onidine (0.75 mg/kg, IP) and naloxone (10 mg/kg, IP), suggesting the i nvolvement of endogenous opioid peptides. The enhanced response to yoh imbine was still present 2 months after ischemia, when preischemic hot plate threshold was restored. AS alpha2-agonists reduce and alpha2-ant agonists increase the outflow of central noradrenaline, it is suggeste d that activation of central noradrenergic systems is involved in the mediation of ischemia-induced analgesia.