Attenuation of defensive analgesia in male mice by 5-HT3 receptor antagonists, ICS 205-930, MDL 72222, MDL 73147EF and MDL 72699.
Recent studies have shown that non-opioid defensive analgesia in male mice is potently inhibited by the 5-HT3 receptor antagonist, ondansetron. The present series of experiments was conducted to further explore the involvement of 5-HT3 receptor mechanisms in this particular form of adaptive inhibition of pain. The drug ICS 205-930 significantly attenuated the reaction at 1.25-2.5 micrograms/kg, with smaller and larger doses being ineffective. Both MDL 72222 and MDL 73147EF produced flat dose-response curves, with significant inhibition of defensive analgesia at minimum effective doses of less than or equal to 10 and 300 micrograms/kg, respectively. Although MDL 72699, the quaternary salt of MDL 72222, also inhibited the reaction, this effect was seen at comparatively large doses (0.5-1.0 mg/kg) only. None of the compounds tested had significant intrinsic effects of tail-flick latencies, over the dose ranges tested. These findings indicate that 5-HT3 receptor mechanisms may have an important modulatory role in certain forms of "stress" analgesia. Data are discussed in relation to the consistent profile of partial inhibition produced by 5-HT3 receptor antagonists in this model.
Rodgers
R J
RJ
Department of Psychology, University of Leeds, U.K.
Shepherd
J K
JK
D000698:Analgesia; D000704:Analysis of Variance; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006358:Hot Temperature; D007211:Indoles / Q000494:pharmacology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D010146:Pain / Q000503:physiopathology*; D011187:Posture; D011807:Quinolizines / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000502:physiology; D012016:Reference Values; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013239:Stereotyped Behavior; D014326:Tropanes / Q000494:pharmacology; D000077526:Tropisetron
D007211:Indoles; D011807:Quinolizines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D014326:Tropanes; D000077526:Tropisetron; C060344:dolasetron; C042253:bemesetron