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 antinociception induced by the repeated administration of opioid antagonists accompanied by exposure to a painful stimulus. The underlying mechanism of this naloxone-induced antinociception (NIA) is still unknown, but the results of several studies suggest that it is a non-opioid response. This study was designed to investigate serotonergic and noradrenergic involvement in NIA. Rats were treated daily with systemic injections of 5 mg/kg naloxone, followed by a 45-s hot plate test of nociception (temperature = 51.5 +/- 0.5 degree C). After rats reached plateau levels of NIA, they received a test trial in which they were treated with various doses of different selective 5-HT or alpha 2 adrenoceptor antagonists 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 showed significant reductions in paw lick latency with respect to rats treated 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 72222, respectively, or by the alpha 2 adrenoceptor blocker idazoxan. None of the 5-HT or alpha 2 adrenoceptor antagonists had any effect on the paw lick latencies of saline-treated rats. A possible role of 5-HT2 receptors in the antinociception induced by opioid receptor blockade is discussed.
Walker
M J
MJ
Addiction Research Foundation, Toronto, Ontario, Canada.
Poulos
C X
CX
Le
A D
AD
D058669:Adrenergic alpha-2 Receptor Antagonists; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D007279:Injections, Subcutaneous; D008297:Male; D009270:Naloxone / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000494:pharmacology*
D058669:Adrenergic alpha-2 Receptor Antagonists; D000700:Analgesics; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D009270:Naloxone