, Volume 91, Issue 3, pp 288–292 | Cite as

Possible neuronal mechanisms involved in neurotensin-induced catalepsy in mice

  • K. Shibata
  • K. Yamada
  • T. Furukawa
Original Investigations


The neuronal mechanisms of neurotensin (NT)-induced catalepsy were investigated in mice. NT administered intracerebroventricularly (ICV 0.5, 1.0 and 2.0 μg) produced catalepsy in a dose-dependent fashion. A significant effect was observed at 2.0 μg and a maximal effect 2–3 h after injection. The NT-induced catalepsy was inhibited by pretreatment with atropine, trihexyphenidyl or biperiden (each drug, 0.8–5.0 mg/kg, IP), anticholinergic drugs, and L-DOPA (100, 200 mg/kg, IP). However, the catalepsy was not significantly antagonized by p-chlorphenylalanine (300 mg/kg×3 days, IP) or methysergide (5, 10 mg/kg, IP), antiserotonergic drugs, and was not potentiated by the GABAergic drugs, aminooxyacetic acid (25 mg/kg, IP) or muscimol (1 mg/kg, IP). In addition, the NT-induced catalepsy was dose-dependently reduced by antihistamines, such as diphenhydramine (0.8–10 mg/kg, IP) and tripelennamine (0.4–5.0 mg/kg, IP) and was potentiated after treatment with histidine (250, 500 mg/kg, IP), a precursor of brain histamine. NT-induced catalepsy was also reduced by ICV pretreatment with diphenhydramine (1–5 μg/rat), a H1 antagonist, but not by cimetidine (5, 20 μg/rat), a H2 antagonist. These findings suggest that the catalepsy induced by NT may involve not only central cholinergic and dopaminergic mechanisms but also a histaminergic mechanism mediated via H1-histamine receptors, and seems to differ from the catalepsy induced by neuroleptics.

Key words

Neurotensin Catalepsy Dopaminergic neurons Cholinergic neurons Histamine Mouse 


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  1. Andén NE (1974) Inhibition of the turnover of the brain dopamine after treatment with gamma-aminobutyrate: 2-oxyglutarate transaminase inhibitor aminooxyacetic acid. Naunyn-Schmiedebergs Arch Pharmacol 283:419–424Google Scholar
  2. Biswas B, Carlsson R (1977) The effects of intracerebroventricularly administered GABA on brain monoamine metabolism. Naunyn-Schmiedebergs Arch Pharmacol 299:41–46Google Scholar
  3. Bowers MB Jr, Roth RH (1972) Interaction of atropine-like drugs with dopamine-containing neurones in rat brain. Br J Pharmacol 44:301–306Google Scholar
  4. Brown J, Handley SL (1980) The development of catalepsy in drug-free mice on repeated testing. Neuropharmacology 19:675–678Google Scholar
  5. Carraway R, Leeman SE (1973) The isolation of a new hypotensive peptide, neurotensin, from bovine hypothalami. J Biol Chem 248:6854–6861Google Scholar
  6. Carraway R, Leeman SE (1976) Radioimmunoassay for neurotensin, a hypothalamic peptide. J Biol Chem 251:7035–7044Google Scholar
  7. Checler F, Vincent JP, Kitabgi P (1983) Neurotensin analogs [D-TYR11] and [D-PHE11] neurotensin resist degradation by brain peptidases in vitro and in vivo. J Pharmacol Exp Ther 227:743–748Google Scholar
  8. Costall B, Naylor RJ (1973) Neuroleptic and non-neuroleptic catalepsy. Arzneimittelforsch 23:674–683Google Scholar
  9. Haley TJ, McCormick WG (1957) Pharmacological effects produced by intracerebral injection of drugs in the conscious mouse. Br J Pharmacol 12:12–15Google Scholar
  10. Iversen LL, Iversen SD, Bloom F, Douglas C, Brown M, Vale W (1978) Calcium-dependent release of somatostatin and neurotensin from rat brain in vitro. Nature 273:161Google Scholar
  11. Jennes L, Stumpf W, Kalivas PW (1982) Neurotensin: Topographical distribution in rat brain by immunohistochemistry. J Comp Neurol 210:211–224Google Scholar
  12. Jolicoeur FB, Barbeau A, Rioux F, Quirion R, St-Pierre S (1981) Differential neurobehavioral effects of neurotensin and structural analogues. Peptides 2:171–175Google Scholar
  13. Kääriänen I (1976) Effects of aminooxyacetic acid and baclofen on the catalepsy and on the increase of mesolimbic and striatal dopamine turnover induced by haloperidol in rats. Acta Pharmacol Toxicol (Copenh) 39:393–400Google Scholar
  14. Kahn D, Hou-Yu A, Zimmerman EA (1982) Localization of neurotensin in the hypothalamus. Ann NY Acad Sci 400:117–131Google Scholar
  15. Kamei C, Dabasaki T, Tasaka K (1983) Cataleptic effect of histamine induced by intraventricular injection in mice. Jpn J Pharmacol 33:1081–1084Google Scholar
  16. Kameyama T, Ukai M (1983) Multi-dimensional analyses of behavior in mice treated with morphine, endorphins and (destyrosines)-gamma-endorphin. Pharmacol Biochem Behav 19:671–677Google Scholar
  17. Klemm WR (1985) Evidence for a cholinergic role in haloperidol-induced catalepsy. Psychopharmacology 85:139–142Google Scholar
  18. Kostowski W, Gumulka W, Czlonkowski A (1972) Reduced cataleptogenic effects of some neuroleptics in rats with lesioned midbrain raphe and treated with parachlorophenylalanine. Brain Res 48:443–446Google Scholar
  19. Lazarus LH, Brown MR, Perrin MH (1977) Distribution, localization and characteristics of neurotensin binding sites in the rat brain. Neuropharmacology 16:625–629Google Scholar
  20. Leslie GB, Maxwell Dr (1964) Some pharmacological properties of thioproperazine and their modification by anti-parkinsonian drugs. Br J Pharmacol 22:301–317Google Scholar
  21. Morpurgo C, Theobald W (1964) Influence of antiparkinson drugs and amphetamine on some pharmacological effects of phenothiazine derivatives used as neuroleptics. Psychopharmacologia 6:178–191Google Scholar
  22. Nemeroff CB (1980) Neurotensin: Perchance an endogenous neuroleptic? Biol Psychiatry 15:283Google Scholar
  23. Nemeroff CB, Bissette G, Prange AJ Jr, Loosen PT, Barlow TS, Lipton MA (1977) Neurotensin: Central nervous system effects of a hypothalamic peptide. Brain Res 128:485–496Google Scholar
  24. Nemeroff CB, Bissette G, Manberg PJ, Osbahr AJ III, Breese GR, Prange AJ Jr (1980) Neurotensin-induced hypothermia: Evidence for an interaction with dopaminergic systems and the hypothalamic-pituitary-thyroid axis. Brain Res 195:69–84Google Scholar
  25. Nemeroff CB, Luttinger D, Hernandez DE, Mailman RB, Mason GA, Davis SD, Widerlov E, Frye GD, Kilts CA, Beaumont K, Breese GR, Prange AJ Jr (1983) Interactions of neurotensin with brain dopamine systems: Biochemical and behavioral studies. J Pharmacol Exp Ther 225:337–345Google Scholar
  26. Nowak JZ, Pilc A, Lebrecht U, Maslinski C (1977) Does histamine interact with cholinergic neurones in its cataleptogenic action in the rat? Neuropharmacology 16:841–847Google Scholar
  27. Osbahr AJ III, Nemeroff CB, Manberg PJ, Prange AJ Jr (1979) Centrally administered neurotensin: Activity in the Julou-Courvoisier muscle relaxation test in mice. Eur J Pharmacol 54:299–302Google Scholar
  28. Sawada S, Takada S, Yamamoto C (1980) Electrical activity recorded from thin sections of bed nucleus of the stria terminalis and the effects of neurotensin. Brain Res 188:578–581Google Scholar
  29. Schaumann W, Kurbjuweit HG (1961) Beeinflussung verschiedener Wirkungen von Thiopropazat durch ein zentrales stimulans. Arzneimittelforsch 11:343–350Google Scholar
  30. Schwartz JC, Barbin C, Duchemin AM, Garbarg M, Palacios JM, Quach TT, Rose C (1980) Histamine receptors in the brain: Characterization by binding studies and biochemical effects. In: Pepeu G, Kuhar MJ, Enna SJ (ed) Receptors for neurotransmitters and peptide hormones. Raven, New York, pp 169–182Google Scholar
  31. Siegel S (1956) Nonparametric statistics for the behavioral sciences. The Fisher exact probability test. McGraw-Hill, New York, pp 96–104Google Scholar
  32. Simon P, Malatray J, Boissier JR (1970) Antagonism by amantadine of prochlorpemazine-induced catalepsy. J Pharm Pharmacol 22:546–547Google Scholar
  33. Snijders R, Kramarcy NR, Hurd RW, Nemeroff CB, Dunn AJ (1982) Neurotensin induces catalepsy in mice. Neuropharmacology 21:465–468Google Scholar
  34. Uhl GR, Snyder SH (1976) Regional and subcellular distribution of brain neurotensin. Life Sci 19:1827–1832Google Scholar
  35. Uhl GR, Kuhar MJ, Snyder SH (1977) Neurotensin: Immunohistochemical localization in rat central nervous system. Proc Natl Acad Sci USA 74:4059–4063Google Scholar
  36. Widerlov E, Kilts CD, Mailman RB, Nemeroff CB, McCown TJ, Prange AJ Jr, Breese GR (1982) Increase in dopamine metabolites in rat brain by neurotensin. J Pharmacol Exp Ther 222:1–6Google Scholar
  37. Worms P, Willigens MT, Lloyd KG (1978) GABA involvement in neuroleptic-induced catalepsy. J Pharm Pharmacol 30:716–718Google Scholar
  38. Wyngaarden JB, Seevers MH (1951) The toxic effects of antihistaminic drugs. JAMA 145:277–282Google Scholar
  39. Young WS III, Uhl GU, Kuhar MJ (1978) Iontophoresis of neurotensin in the area of the locus coeruleus. Brain Res 150:431–435Google Scholar
  40. Zetler G (1960) Pharmakologische Eigenschaften antidepressive wirkender Pharmaka. Dtsch Med Wochenschr 85:2276–2281Google Scholar

Copyright information

© Springer-Verlag 1987

Authors and Affiliations

  • K. Shibata
    • 1
  • K. Yamada
    • 2
  • T. Furukawa
    • 2
  1. 1.Research Laboratory of Biodynamics, School of MedicineFukuoka UniversityFukuokaJapan
  2. 2.Department of Pharmacology, School of MedicineFukuoka UniversityFukuokaJapan

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