Involvement of α2-receptors in the analgesia induced by transient forebrain ischemia in rats

Abstract

Transient forebrain ischemia induced in rats by the four-vessel occlusion method produced analgesic effects in the hotplate test that persisted for 2 weeks. Ischemia-induced analgesia was attenuated by low doses of α 2-agonist clonidine (0.01–0.10 mg/kg, IP) and enhanced by low doses of α 2-antagonists yohimbre (1–2 mg/kg, IP) and idazoxan (0.25–1.00 mg/kg, IP) administration 7 days after ischemia. Ischemia-induced analgesia was not affected by methysergide, naloxone, propranolol, 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 clonidine (0.75 mg/kg, IP) and naloxone (10 mg/kg, IP), suggesting the involvement of endogenous opioid peptides. The enhanced response to yohimbine was still present 2 months after ischemia, when preischemic hotplate threshold was restored. As α 2-agonists reduce and α 2-antagonists increases the outflow of central noradrenaline, it is suggested that activation of acti central noradrenergic systems is involved in the mediation of ischemia-induced analgesia.