The peripheral nociceptive actions of intravenously administered 5-HT in the rat requires dual activation of both 5-HT2 and 5-HT3 receptor subtypes.

In 16-week-old Sprague-Dawley rats lightly anesthetized with pentobarbital, 5-HT (3-96 micrograms/kg, i.v.; n = 6) produced distinct pseudaffective responses and a dose-dependent (slope = 17.2 +/- 6.8 s/log10 dose) inhibition of the tail-flick (TF) reflex (ED50 = 32.6 +/- 9.2 micrograms/kg). In the same rats, a 1:1 combination of alpha-methyl 5-HT (a 5-HT2, receptor selective agonist) and 2-methyl 5-HT (a 5-HT3 receptor selective agonist) (3-192 micrograms/kg, i.v.), produced the same profile of pseudaffective responses and also resulted in a dose-dependent (slope = 34.0 +/- 7.0 s/log10 dose) inhibition of the TF reflex (ED50 = 88.4 +/- 20.5 micrograms/kg). In contrast, administration of alpha-methyl 5-HT (3-192 micrograms/kg, i.v.) or 2-methyl 5-HT (3-192 micrograms/kg, i.v.) alone did not produce any pseudaffective responses or any change in TF latency from baseline. In conscious 16-week-old male Sprague-Dawley rats, administration of 5-HT (48 micrograms/kg, i.v.; n = 5), or a 1:1 combination of alpha-methyl 5-HT and 2-methyl 5-HT (total dose = 120 micrograms/kg, i.v.; n = 5), resulted in a passive avoidance behavior assessed in a step-down paradigm (slopes = 139.7 +/- 58.2 and 154.9 +/- 63.9 s/trial, respectively), and the same profile of distinct pseudaffective responses exhibited by the lightly pentobarbital-anesthetized rats.(ABSTRACT TRUNCATED AT 250 WORDS)