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.