Production of serotonin syndrome by 8-OH DPAT in Cryptotis parva.
We have previously shown that the 5-HT2A/C agonist, DOI, potently and in a dose-dependent manner produces the head-twitch response in the least shrew (Cryptotis parva) via the activation of serotonergic 5-HT2A receptors. The purpose of the present study was to determine whether activation of 5-HT1A receptors by its selective agonist, 8-OH DPAT, can induce the serotonin syndrome (SS) in this species. In the rat, the symptoms of SS include: forepaw splaying, hindleg abduction, forepaw treading, flat body posture, tremor, and straub tail. Intraperitoneal (i.p.) administration of 8-OH DPAT produced four classic symptoms (forepaw splaying, hindleg abduction, forepaw treading, and straub tail) of SS in the least shrew in a dose-dependent manner in the 30-min observation period. The mean total cumulative score for all components of SS also significantly increased in intensity in a dose-dependent fashion. Administration of selective 5-HT1A antagonists [S(-)UH 301 or NAN-190] potently blocked the 8-OH DPAT-induced mean total SS score in a dose-dependent manner. Moreover, these antagonists had similar potencies as indicated by their identical ID50 values (0.5 and 0.52 mg/kg respectively). However, unexpectedly and unlike the published findings in the rat, the nonselective 5-HT1A antagonist with b-blocking activity, propranolol, failed to attenuate the induced response in this species. As was expected, the selective 5-HT2A/C antagonist, SR 46349B, did not affect the intensity 8-OH DPAT-induced symptoms. Overall, these data suggest that the SS produced by 8-OH DPAT in the least shrew is mediated via the activation of serotonergic 5-HT1A receptors. In addition, propranolol is not a useful 5-HT1A antagonist in this species.
Darmani
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NA
Department of Pharmacology, Kirksville College of Osteopathic Medicine, MO 63501, USA. Nissard@fileserver5.KCOM.edu
Zhao
W
W
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000031:analogs & derivatives / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D005464:Fluorobenzenes / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D008297:Male; D010636:Phenols / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D020230:Serotonin Syndrome / Q000139:chemically induced* / Q000523:psychology*; D012788:Shrews / Q000502:physiology*
D000319:Adrenergic beta-Antagonists; D005464:Fluorobenzenes; D010636:Phenols; D010879:Piperazines; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C058895:1-(2-methoxyphenyl)-4-(4-(2-phthalimido)butyl)piperazine; C064282:UH 301; C076033:SR 46349B; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D011433:Propranolol