Hyperthermia induced by m-trifluoromethylphenylpiperazine (TFMPP) or m-chlorophenylpiperazine (m-CPP) in heat-adapted...

TFMPP and m-CPP, non-selective 5-HT agonists, administered in doses of 1-20 mg/kg evoked hyperthermia in rats at a high ambient temperature (28 degrees C). The hyperthermic effect of TFMPP (10 mg/kg) or m-CPP (10 mg/kg) was dose-dependently antagonized by the 5-HT1c and 5-HT2 receptor antagonists mesulergine (0.5-4 mg/kg), ketanserin (0.6-2.5 mg/kg) and ritanserin (0.5-2 mg/kg) and by the non-selective 5-HT antagonist metergoline (0.5-1 mg/kg), or was attenuated by the 5-HT1A, 5-HT2 and dopamine receptor antagonist spiperone (3 mg/kg, but not 0.3 or 1 mg/kg). On the other hand, the 5-HT1A, 5-HT1B and beta adrenoceptor antagonists pindolol (2 mg/kg) and cyanopindolol (2 mg/kg), the 5-HT1A receptor agonist/antagonist ipsapirone (10 and 35 mg/kg) and haloperidol (0.25 and 0.5 mg/kg) showed a tendency towards enhancing the TFMPP- or m-CPP-induced hyperthermia. The 5-HT1A and alpha 1-adrenoceptor antagonist NAN-190 (1-4 mg/kg), the 5-HT3 antagonists tropisetron (0.01-1 mg/kg) and zacopride (0.5 and 1 mg/kg), the beta-blockers betaxolol (8 mg/kg) and ICI 118, 551 (8 mg/kg), which have no affinity for 5-HT receptors and prazosin (1 mg/kg), did not affect the hyperthermic effect of TFMPP or m-CPP. The hyperthermias studied were not modified, in animals with 5-HT lesion produced by p-chloroamphetamine (PCA) either. All the drugs used as putative receptor antagonists, as well as PCA, did not change or decreased (ipsapirone) the body temperature in heat-adapted rats.(ABSTRACT TRUNCATED AT 250 WORDS)