EFFECTS OF ACUTE SELECTIVE 5-HT1, 5-HT2, 5-HT3 RECEPTOR AND ALPHA(2) ADRENOCEPTOR BLOCKADE ON NALOXONE-INDUCED ANTINOCICEPTION

Several studies have demonstrated a paradoxical form of antinociceptio n induced by the repeated administration of opioid antagonists accompa nied by exposure to a painful stimulus. The underlying mechanism of th is naloxone-induced antinociception (NIA) is still unknown, but the re sults of several studies suggest that it is a non-opioid response. Thi s study was designed to investigate serotonergic and noradrenergic inv olvement in NIA. Rats were treated daily with systemic injections of 5 mg/kg naloxone, followed by a 45-s hot plate test of nociception (tem perature = 51.5 +/- 0.5 degrees C). After rats reached plateau levels of NIA, they received a test trial in which they were treated with var ious doses of different selective 5-HT or alpha(2) adrenoceptor antago nists in addition to naloxone before the hot plate test. Rats treated with 0.16, 0.32 and 0.63 mg/kg pirenperone or 2.5 mg/kg ritanserin sho wed significant reductions in paw lick latency with respect to rats tr eated with vehicle. In addition, high doses of yohimbine (7.5-10 mg/kg ) also effectively reversed NIA. In contrast, NIA was not affected by acute blockade of 5-HT1 or 5-HT3 receptors by methiothepin or MDL 7222 2, respectively, or by the alpha(2) adrenoceptor blocker idazoxan. Non e of the 5-HT or alpha(2) adrenoceptor antagonists had any effect on t he paw lick latencies of saline-treated rats. A possible role of 5-HT2 receptors in the antinociception induced by opioid receptor blockade is discussed.