TY - JOUR
T1 - The antinociceptive effect of trazodone in mice is mediated through both μ-opioid and serotonergic mechanisms
AU - Schreiber, Shaul
AU - Backer, Maria M.
AU - Herman, Isachar
AU - Shamir, David
AU - Boniel, Tal
AU - Pick, Chaim G.
PY - 2000/9/1
Y1 - 2000/9/1
N2 - The antinociceptive effects of trazodone (a triazolopyridine derivative with antidepressant activity) and its interaction with various opioid, noradrenaline and serotonin receptor subtypes were evaluated. Mice were tested with a hotplate analgesia meter. Trazodone induced a dose-dependent antinociceptive effect following i.p. administration. The ED50 for mice in the hotplate assay for trazodone was 24.8 mg/kg (9.8; 67.4; 95% CL). The effect of opioid, adrenergic and serotonergic receptor antagonists was examined as to their ability to block trazodone antinociception. Trazodone- induced antinociception was significantly inhibited by naloxone, β-FNA and naloxonazine, but not by nor-BNI or naltrindole, implying involvement of μ1- and μ2-opioid mechanisms. When adrenergic and serotonergic antagonists were used, metergoline (p < 0.05) but not phentolamine or yohimbine, decreased antinociception elicited by trazodone, implying a clear 5-HT mechanism of antinociception. When trazodone was administered together with various agonists of the opioid receptor subtypes, it significantly potentiated antinociception mediated by μ1- and μ2-opioid receptor subtypes. Summing up these results, we conclude that the antinociceptive effect of trazodone is mainly influenced by the μ1- + μ2-opioid receptor subtype combined with the serotonergic receptor. These results explain the diffuse clinical use of trazodone in the management of some pain syndromes, and in opioid- and alcohol-detoxification programs, but raise questions regarding a possible 'indirect' opioid-dependence induced by trazodone itself. (C) 2000 Elsevier Science B.V.
AB - The antinociceptive effects of trazodone (a triazolopyridine derivative with antidepressant activity) and its interaction with various opioid, noradrenaline and serotonin receptor subtypes were evaluated. Mice were tested with a hotplate analgesia meter. Trazodone induced a dose-dependent antinociceptive effect following i.p. administration. The ED50 for mice in the hotplate assay for trazodone was 24.8 mg/kg (9.8; 67.4; 95% CL). The effect of opioid, adrenergic and serotonergic receptor antagonists was examined as to their ability to block trazodone antinociception. Trazodone- induced antinociception was significantly inhibited by naloxone, β-FNA and naloxonazine, but not by nor-BNI or naltrindole, implying involvement of μ1- and μ2-opioid mechanisms. When adrenergic and serotonergic antagonists were used, metergoline (p < 0.05) but not phentolamine or yohimbine, decreased antinociception elicited by trazodone, implying a clear 5-HT mechanism of antinociception. When trazodone was administered together with various agonists of the opioid receptor subtypes, it significantly potentiated antinociception mediated by μ1- and μ2-opioid receptor subtypes. Summing up these results, we conclude that the antinociceptive effect of trazodone is mainly influenced by the μ1- + μ2-opioid receptor subtype combined with the serotonergic receptor. These results explain the diffuse clinical use of trazodone in the management of some pain syndromes, and in opioid- and alcohol-detoxification programs, but raise questions regarding a possible 'indirect' opioid-dependence induced by trazodone itself. (C) 2000 Elsevier Science B.V.
KW - Antidepressants
KW - Antinociception
KW - Hotplate
KW - Opioid receptor subtypes
KW - Pain
KW - Serotonin
KW - Trazodone
UR - http://www.scopus.com/inward/record.url?scp=0034283098&partnerID=8YFLogxK
U2 - 10.1016/S0166-4328(00)00185-6
DO - 10.1016/S0166-4328(00)00185-6
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AN - SCOPUS:0034283098
SN - 0166-4328
VL - 114
SP - 51
EP - 56
JO - Behavioural Brain Research
JF - Behavioural Brain Research
IS - 1-2
ER -