Involvement of serotonergic receptor subtypes in the production of antinociception by psychological stress in mice.
Besides the important role of emotional factors in the production of psychological-stress-induced analgesia (PSY-SIA), recent attention to the participation of serotonergic (5-HTnergic) neurons in the fear- and anxiety-evoking mechanism led us to examine the effects of 5-HTnergic ligands on PSY-SIA. Pretreatment of mice with 2.0 to 10 mg/kg of methysergide, a 5-HT receptor antagonist, or 1.0 to 10 mg/kg of buspirone, a 5-HT1A receptor partial agonist, dose-dependently suppressed the production of PSY-SIA. Ritanserin, a 5-HT2 receptor antagonist, 1.0 to 5.0 mg/kg, or Y-25,130, a 5-HT3 receptor antagonist, 0.03 and 0.1 mg/kg, also inhibited PSY-SIA dose-dependently, while (+/-)pindolol, a 5-HT1A/1B receptor antagonist, was ineffective at doses up to 3.0 mg/kg. Furthermore, the suppressive effect of PSY-stress on the development of antinociceptive tolerance to morphine was also antagonized by methysergide, buspirone, ritanserin and Y-25,130, but not by (+/-)pindolol. These results suggest that 5-HT receptor (5-HT1A, 5-HT2 and 5-HT3 but not 5-HT1B)-mediated mechanisms play an important role in the production of PSY-SIA.
Tokuyama
S
S
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Nagasaki University, Japan.
Takahashi
M
M
Kaneto
H
H
D000818:Animals; D002065:Buspirone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D010146:Pain / Q000503:physiopathology*; D010869:Pindolol / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013315:Stress, Psychological / Q000503:physiopathology*
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D009020:Morphine; D010869:Pindolol; D002065:Buspirone