Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Hyperthermia induced bym-trifluoromethylphenylpiperazine (TFMPP) orm-chlorophenylpiperazine (m-CPP) in heat-adapted rats

  • 16 Accesses

  • 25 Citations


TFMPP andm-CPP, non-selective 5-HT agonists, administered in doses of 1–20 mg/kg evoked hyperthermia in rats at a high ambient temperature (28°C). The hyperthermic effect of TFMPP (10 mg/kg) orm-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 andβ 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- orm-CPP-induced hyperthermia. The 5-HT1A and α1-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), theβ-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 orm-CPP. The hyperthermias studied were not modified, in animals with 5-HT lesion produced byp-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. The obtained results suggest that the hyperthermia induced by TFMPP orm-CPP is mediated by 5-HT2, and maybe also by 5-HT1c receptors — those which are located postsynaptically.

This is a preview of subscription content, log in to check access.


  1. Auerbach SB, Kamalakannan N, Rutter JJ (1990) TFMPP and RU24969 enhance serotonin release from rat hippocampus 190:51–57

  2. Bradley PB, Engel G, Feniuk W, Fozard JR, Humphrey PPA, Middlemiss DN, Mylecharane EJ, Richardson BP, Saxena PR (1986) Proposal for the classification and nomenclature of functional receptors for 5-hydroxytryptamine. Neuropharmacology 25:563–576

  3. Chojnacka-Wójcik E, Tatarczyńska E, Gołembiowska K, Przegaliński E (1991) Involvement of 5-HT1A receptors in the antidepressant-like activity of gepirone in the forced swimming test in rats. Neuropharmacology 30:711–717

  4. Conn PJ, Sanders-Bush E (1987) Relative efficacies of piperazines at the phosphoinositide hydrolysis-linked serotonergic (5-HT2 and 5-HT1C) receptors. J Pharmacol Exp Ther 242:552–557

  5. Dumuis A, Bouheal R, Sebben M, Cory R, Bockaert J (1988) A non-classical 5-hydroxytryptamine receptor positively coupled with adenylate cyclase in the central nervous system. Mol Pharmacol 34:880–887

  6. Engel G, Gothert M, Hoyer D, Schlicker E, Hillenbrand K (1986) Identity of inhibitory presynaptic 5-hydroxytryptamine (5-HT) autoreceptors in the rat brain cortex with 5-HT1B binding sites. Naunyn-Schmiedeberg's Arch Pharmacol 332:1–7

  7. Glennon RA, Naiman NA, Pierson ME, Titeler M, Lyon RA, Weisberg E (1988) NAN-190: an arylpiperazine analog that antagonizes the stimulus effects of the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT). Eur J Pharmacol 154:339–341

  8. Gudelsky GA, Koenig JI, Meltzer HY) (1986 Thermoregulatory responses to serotonin (5-HT) stimulation in the rat. Evidence for opposing roles of 5-HT2 and 5-HT1A receptors. Neuropharmacology 25:1307–1313

  9. Heuring RE, Peroutka SJ (1987) Characterization of a novel3H-5-hydroxytryptamine binding site subtype in bovine brain membranes. J Neurosci 7:894–903

  10. Hjorth S, Carlsson A (1986) Is pindolol a mixed agonist-antagonist at central serotonin (5-HT) receptors? Eur J Pharmacol 129:131–138

  11. Hjorth S, Sharp T (1990) Mixed agonist/antagonist properties of NAN-190 at 5-HT1A receptors: behavioural and in vivo brain microdialysis studies. Life Sci 46:955–963

  12. Hoyer D (1988) Functional correlates of serotonin 5-HT1 recognition sites. J Recept Res 8:59–81

  13. Hoyer D (1989) 5-Hydroxytryptamine receptors and effector coupling mechanisms in peripheral tissues. In: Fozard JR (ed) The peripheral action of 5-hydroxytryptamine. Oxford University Press, Oxford, pp 72–99

  14. Hoyer D, Engel G, Kalkman HO (1985) Molecular pharmacology of 5-HT1 and 5-HT2 recognition sites in rat and pig brain membranes. Radioligand binding studies with [3H] 5-HT, [3H] 8-OH-DPAT, (−)[125I] iodocyanopindolol, [3H] mesulergine and [3H] ketanserin. Eur J Pharmacol 118:13–23

  15. Kennet GA, Curzon G (1988) Evidence that mCPP may have behavioural effects mediated by central 5-HT1C receptors. Br J Pharmacol 94:137–147

  16. Kłodzińska A, Jaros T, Chojnacka-Wójcik E, Maj J (1989) Exploratory hypoactivity induced bym-trifluoromethylphenylpiperazine (TFMPP) andm-chlorophenylpiperazine (m-CPP). J Neural Transm 1:207–218

  17. Korstanje C, Sprenkels R, Doods HN, Hugtenburg JG, Boddeke E, Batink HD, Thoolen MJMC, Van Zwieten PA (1986) Characterization of flufylline, fluprofylline, ritanserin, butanserin and R 56413 with respect to in-vivo α1-, α2- and 5-HT2-receptor antagonism and in-vitro α1-, α2- and 5-HT2-receptors: comparison with ketanserin. J Pharm Pharmacol 38:374–379

  18. Leysen JE (1990) Gaps and peculiarities in 5-HT2 receptor studies. Neuropsychopharmacology 3:361–369

  19. Maj J, Lewandowska A (1980) Central serotoninmimetic action of phenylpiperazines. Pol J Pharmacol Pharm 32:495–504

  20. Maj J, Baran L, Bigajska K, Rogóż Z, Skuza G (1978) The influence of neuroleptics on the behavioural effect of 5-hydroxytryptophan. Pol J Pharmacol Pharm 30:431–440

  21. Maj J, Chojnacka-Wójcik E, Tatarczyńska E, Kłodzińska A (1987) Central action of ipsapirone, a new anxiolytic drug, on serotoninergic, noradrenergic and dopaminergic functions. J Neural Transm 70:1–17

  22. Maj J, Chojnacka-Wójcik E, Kłodzińska A, Dereń A, Moryl E (1988) Hypothermia induced by m-trifluoromethylphenylpiperazine orm-chlorophenylpiperazine: an effect mediated by 5-HT1B receptors. J Neural Transm 73:43–55

  23. Maura G, Ulivi M, Raiteri M (1987) (−)-Propranolol and (±)-cyanopindolol are mixed agonists-antagonists at serotonin auto receptors in the hippocampus of the rat brain. Neuropharmacology 26:713–717

  24. Middlemiss DN, Fozard JR (1983) 8-Hydroxy-2-(di-n-propylamino)-tetralin discriminates between subtypes of 5-HT1 recognition sites. Eur J Pharmacol 90:151–153

  25. Pawłowski L (1984) Amitryptyline and femoxetine, but not clomipramine or citalopram, antagonize hyperthermia induced by directly acting 5-hydroxytryptamine-like drugs in heat adapted rats. J Pharm Pharmacol 36:197–199

  26. Pedigo NW, Yamamura HI, Nelson DL (1981) Discrimination of multiple3H-5-hydroxytryptamine binding site by the neuroleptic spiperone in the rat brain. J Neurochem 36:220–226

  27. Pettibone DJ, Williams M (1984) Serotonin-releasing effects of substituted piperazines in vitro. Biochem Pharmacol 33:1531–1535

  28. Przegaliński E, Ismaiel AM, Chojnacka-Wójcik E, Budziszewska B, Tatarczyńska E, Błaszczyńska E (1990) The behavioural, but not the hypothermic or corticosterone, response to 8-hydroxy-2-(di-n-propylamino) tetralin, is antagonized by NAN-190 in the rat. Neuropharmacology 29:521–526

  29. Richardson BP, Engel G, Donatsch P, Stadler PA (1985) Identification of serotonin M-receptor subtypes and their specific blockade by a new class of drugs. Nature 316:126–131

  30. Sahin-Erdemli I, Schoeffter P, Hoyer D (1991) Competitive antagonism by recognised 5-HT2 receptor antagonists at 5-HT1C in pig choroid plexus. Naunyn-Schmiedeberg's Arch Pharmacol 344:137–142

  31. Sanders-Bush E, Breeding M (1988) Putative selective 5-HT2 antagonists block serotonin 5-HT1C receptors in the choroid plexus. J Pharmacol Exp Ther 247:169–173

  32. Sheldon PW, Aghajanian GK (1991) Excitatory responses to serotonin (5-HT) in neurons of the rat piriform cortex: evidence for mediation by 5-HT1C receptors in pyramidal cells and 5-HT2 receptors in interneurons. Synapse 9:208–218

  33. Sills MA, Wolfe PP, Frazer A (1984) Determination of selective and nonselective compounds for the 5-HT1A and 5-HT1B receptor subtypes in rat frontal cortex. J Pharmacol Exp Ther 231:480–487

  34. Simansky KJ, Schechter LE (1988) Properties of some 1-arylpiperazines as antagonists of stereotyped behaviors mediated by central serotonergic receptors in rodents. J Pharmacol Exp Ther 247:1073–1081

  35. Smith LM, Peroutka SJ (1986) Differential effects of 5-hydroxytryptamine1A selective drugs on the 5-HT behavioral syndrome. Pharmacol Biochem Behav 24:1513–1519

  36. Smith WW, Sancilio LF, Owera-Atepo JB, Naylor RJ, Lambert L (1988) Zacopride, a potent 5-HT3 antagonist. J Pharm Pharmacol 40:301–302

  37. Tricklebank MD, Forler C, Fozard JR (1984) The involvement of subtypes of the 5-HT1 receptor and of catecholaminergic systems in the behavioural response to 8-hydroxy-2-(di-n-propylamino)-tetralin in the rat. Eur J Pharmacol 106:271–282

  38. Tricklebank MD, Forler C, Middlemiss DN, Fozard JR (1985) Subtypes of the 5-HT receptor mediating the behavioural responses to 5-methoxy-N, N-dimethyltryptamine in the rat. Eur J Pharmacol 117:15–24

Download references

Author information

Correspondence to A. Kłodzińska.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Kłodzińska, A., Chojnacka-Wójcik, E. Hyperthermia induced bym-trifluoromethylphenylpiperazine (TFMPP) orm-chlorophenylpiperazine (m-CPP) in heat-adapted rats. Psychopharmacology 109, 466–472 (1992).

Download citation

Key words

  • Hyperthermia
  • m-CPP
  • 5-HT-receptor antagonists