Psychopharmacology

, Volume 114, Issue 4, pp 651–656 | Cite as

Effects of (R)-α-methylhistamine and scopolamine on spatial learning in the rat assessed using a water maze

  • C. P. S. Smith
  • A. J. Hunter
  • G. W. Bennett
Original Investigations

Abstract

The effects of (R)-α-methylhistamine ((R)-α-MeHA, a selective H3-receptor agonist) and scopolamine (SCOP, a muscarinic antagonist) were investigated on spatial learning and memory in the rat (Hooded Lister) using a water maze (WM). (R)-α-MeHA treatment (6.3 and 10 mg/kg IP) had no apparent effect on spatial learning but did result in enhanced spatial recall at the higher dose, assessed by a transfer (probe) test after training. In contrast, SCOP (0.5 mg/kg IP) induced a learning and memory deficit measured both during and after training. In animals treated with (R)-α-MeHA and SCOP, (R)-α-MeHA partially (6.3 mg/kg) and completely (10 mg/kg) reversed the SCOP-induced deficit during the training phase, while in the post-training transfer test, (R)-α-MeHA (10 mg/kg) significantly reduced the SCOP-induced memory deficit. None of the treatments described resulted in impaired visual acuity as demonstrated by a raised platform test. These results are consistent with a role for histamine in cognitive processes and suggest a possible interaction between central histamine and cholinergic mechanisms associated with rodent spatial learning and memory.

Key words

(R)-α-Methylhistamine Scopolamine Histamine Cognition Water maze Rat 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Arrang JM, Garbarg M, Schwartz JC (1983) Autoinhibition of brain histamine release mediated by a novel class (H3) of histamine receptor. Nature 302:832–837Google Scholar
  2. Arrang JM, Garbarg M, Schwartz JC (1985) Autoregulation of histamine release in brain by presynaptic H3-receptors. Neuroscience 15:553–562Google Scholar
  3. Arrang JM, Garbarg M, Lancelot JC, Lecomte JM, Pollard H, Robba M, Schunack W, Schwartz JC (1987) Highly potent and selective ligands for histamine H3-receptors. Nature 327:117–123Google Scholar
  4. Arrang JM, Devaux B, Chodkiewicz JP, Schwartz JC (1988) H3-receptors control histamine release in human brain. J Neurochem 51:105–108Google Scholar
  5. Bristow LJ, Bennett GW (1988) A role for histamine H3 receptors in histamine-induced hypoactivity in the rat. Br J Pharmacol 94:319PGoogle Scholar
  6. Buresova O, Bulhuis JJ, Bures J (1986) Differential effects of cholinergic blockade on performance of rats in the water tank navigation task and in a radial arm maze. Behav Neurosci 100:476–482Google Scholar
  7. Caine ED, Weingartner H, Ludlow DL, Cudahy EA, Wehry S (1981) Qualitative analysis of scopolamine-induced amnesia. Psychopharmacology 74:74–80Google Scholar
  8. Cheal ML (1981) Scopolamine disrupts maintenance of attention rather than memory processes. Behav Neural Biol 33:163–187Google Scholar
  9. Clapham J, Kilpatrick G (1992) Histamine H3 receptors modulate the release of [3H]-acetylcholine from slices of rat entorhinal cortex: evidence for the possible existence of H3 receptor subtypes. Br J Pharmacol 197:919–923Google Scholar
  10. Clapham J, Kilpatrick GJ (1993) Histamine H3 receptor-mediated modulation of water consumption in the rat. Br J Pharmacol 232:99–103Google Scholar
  11. Coughlan J, Costall B, Kelly ME, Naylor RJ, Tyers MB (1991) Ondansetron attenuates scopolamine deficit in a water maze task. Br J Pharmacol 101:562PGoogle Scholar
  12. Cumming P, Shaw C, Vincent SR (1991) High affinity histamine binding site is the H3 receptor: characterization and autoradiographic localization in the rat brain. Synapse 8:144–151Google Scholar
  13. De Almeida M, Izquierdo I (1986) Memory facilitation by histamine. Arch Int Pharmacodyn Ther 283:193–198Google Scholar
  14. De Almeida M, Izquierdo I (1989) Intracerebroventricular histamine, but not 48/80, causes posttraining memory facilitation in the rat. Arch Int Pharmacodyn Ther 291:202–207Google Scholar
  15. Decker MW, McGaugh JL (1991) The role of interactions between the cholinergic system and other neuromodulary systems in learning and memory. Synapse 7:151–168Google Scholar
  16. Everitt BJ, Robbins TW, Selden NRW (1990) Functions of the locus coeruleus noradrenergic system: a neurobiological and behavioural synthesis. In: Heal DJ, Marsden CA (eds) The pharmacology of noradrenaline in the central nervous system. Oxford University Press, Oxford, pp 349–378Google Scholar
  17. Fink K, Schlicker E, Neise A, Göthert M (1990) Involvement of presynaptic H3 receptors in the inhibitory effect of histamine on serotonin release in the rat brain cortex. Naunyn-Schmiedeberg's Arch Pharmacol 342:513–519Google Scholar
  18. Garbarg M, Trung Tuong MD, Gros C, Schwartz JC (1989) Effects of histamine H3-ligands on various biochemical indices of histaminergic neuron activity in rat brain. Eur J Pharmacol 164:1–11Google Scholar
  19. Gower AJ (1992) 5-HT receptors and cognitive function. In: Marsden CA, Heal DL (eds) Frontiers in pharmacology and therapeutics. Blackwell, Oxford, pp 239–259Google Scholar
  20. Gulat-Marnay C, Lafitte A, Arrang JM, Schwartz JC (1989) Regulation of histamine release and synthesis in the brain by muscarinic receptors. J Neurochem 52:248–254Google Scholar
  21. Hagan JJ, Morris RGM (1988) The cholinergic hypothesis of memory; a review of animal experiments. In: Iversen LL, Iversen SD, Snyder SH (eds) Handbook of psychopharmacology. Plenum, New York, pp 237–323Google Scholar
  22. Hunter AJ, Roberts F, Tutty CA (1986) Scopolamine impairs performance in the Morris water maze in both naive and trained rats. Br J Pharmacol 87:41PGoogle Scholar
  23. Hunter J (1991) Cholinergic drugs and memory in animals. In: Weinman J, Hunter J (eds) Memory: neurochemical and abnormal perspectives. Harwood, Glasgow, pp 43–65Google Scholar
  24. Itoh Y, Oishi R, Nishibori M, Saeki K (1991) Characterization of histamine release from the rat hypothalamus as measured by α-fluromethylhistidine-induced decrease. Jpn J Pharmacol 51:581–584Google Scholar
  25. Itoh Y, Oishi R, Adachi N, Saeki K (1992) A highly sensitive assay for histamine using ion-pair HPLC coupled with postcolumn fluorescent derivatization: its application to biological specimens. J Neurochem 58:884–889Google Scholar
  26. Kamei C, Tasaka K (1991) Participation of histamine in the stepthrough active avoidance response and its inhibition by H1-blockers. Jpn J Pharmacol 57:473–482Google Scholar
  27. Kopelman MD (1986) The cholinergic neurotransmitter system in human memory and dementia: a review. Q J Exp Psychol 38A:535–573Google Scholar
  28. Lin JS, Sakai K, Vanni-Mercier G, Arrang JM, Garbarg M, Schwartz JC, Jouvet M (1990) Involvement of histamine in arousal mechanisms demonstrated with H3-receptor ligands in the cat. Brain Res 523:325–330Google Scholar
  29. Martinez-Mir MI, Pollard H, Moreau J, Arrang JM, Ruat M, Traiffort E, Schwartz JC, Palacios JM (1990) Three histamine receptors (H1, H2 and H3) visualized in the brain of human and non-human primates. Brain Res 526:322–327Google Scholar
  30. Mochizuki T, Yamatodani A, Okakura K, Horii A, Inagaki N, Wada H (1991) Circadian rhythm of histamine release from the hypothalamus of freely moving rats. Physiol Behav 51:391–394Google Scholar
  31. Molchan SE, Martinez RA, Hill JL, Weingartner HJ, Thompson K, Vitiello B, Sunderland T (1992) Increased cognitive sensitivity to scopolamine with age and a perspective on the scopolamine model. Brain Res Rev 17:215–226Google Scholar
  32. Monti JM, Jantos H, Boussard M, Altier H, Orellana C, Olivera S (1991) Effects of selective activation or blockade of the histamine H3 receptor on sleep and wakefulness. Eur J Pharmacol 205:283–287Google Scholar
  33. Morris RGM (1981) Spatial localization does not require the presence of local cues. Learn Motiv 12:239–260Google Scholar
  34. Morris RGM (1984) Development of a water-maze procedure for studying spatial learning in the rat. J Neurosci Methods 11:47–60Google Scholar
  35. Oishi R, Itoh Y, Nishibori M, Saeki K (1989) Effects of the histamine H3-agonist (R)-α-methylhistamine and the antagonist thioperamide on histamine metabolism in the mouse and rat brain. J Neurochem 52:1388–1392Google Scholar
  36. Oishi R, Nishibori M, Otoh Y, Shishido S, Saeki K (1990) Is monoamine turnover in the brain regulated by histamine H3 receptors? Eur J Pharmacol 184:135–142Google Scholar
  37. Ono Y, Yamatodani A, Kishino J, Okada S, Wada H (1992) Cholinergic influence of K+-evoked release of endogenous histamine from rat hypothalamic slices in vitro. Methods Find Exp Clin Pharmacol 14:35–40Google Scholar
  38. Pollard H, Moreau J, Arrang JM, Schwartz JC (1993) A detailed autoradiographic mapping of histamine H3 receptors in rat brain areas. Neuroscience 52:169–189Google Scholar
  39. Ray PG, Meador KJ, Loring EW, Zamrini XH, Buccafusco JJ (1992) Central anticholinergic hypersensitivity in aging. J Geriatr Psychiatr. Neurol 5:72–77Google Scholar
  40. Reikkinen P, Sirvio J, Ekonsalo T, Reikkinen P (1992) Effects of noradrenergic DSP4 lesion on the effectiveness of pilocarpine in reversing scopolamine-induced amnesia. Brain Res Bull 28:919–922Google Scholar
  41. Sakai N, Onodera K, Maeyama K, Yanai K, Watanabe T (1991) Effects of thioperamide, a histamine H3 receptor antagonist, on locomotor activity and brain histamine content in mast celldeficient W/Wv mice. Life Sci 48:2397–2404Google Scholar
  42. Sakai N, Onodera K, Maeyama K, Yanai K, Watanabe T (1992) Effects of (S)-α-fluoromethylhistidine and metoprine on locomotor activity and brain histamine content in mice. Life Sci 51:397–405Google Scholar
  43. Schlicker E, Fink K, Hinterthaner M, Gothert M (1989) Inhibition of noradrenaline release in the rat brain cortex via presynaptic H3 receptors. Naunyn-Schmiedeberg's Arch Pharmacol 430:633–638Google Scholar
  44. Schlicker E, Glaser T, Lummen G, Neise A, Gothert M (1991) Serotonin and histamine receptor-mediated inhibition of serotonin and noradrenaline release in rat brain cortex under nimodipine treatment. Neurochem Int 19:437–444Google Scholar
  45. Schlicker E, Behling A, Lummen G, Malinowska B, Gothert M (1992) Mutual interaction of histamine H3 receptors and α2-adrenoceptors on noradrenergic terminals in mouse and rat brain cortex. Naunyn-Schmiedeberg's Arch Pharmacol 345:639–646Google Scholar
  46. Schwartz JC, Garbag M, Pollard H (1986) Histaminergic transmission in the brain. In: Mountcastle VB, Bloom FE, Geiger SR (eds) Handbook of physiology. Waverly Press, Bethesda, pp 257–316Google Scholar
  47. Schwartz JC, Arrang JM, Garbarg M, Pollard H, Ruat M (1991) Histaminergic transmission in the mammalian brain. Physiol Rev 71:1–53Google Scholar
  48. Smith CPS, Hunter AJ, Bennett GW (1993) Effects of (R)-α-methylhistamine and scopolamine on water maze performance in the rat. Br J Pharmacol 108:80PGoogle Scholar
  49. Warburton DM, Rusted JM (1991) Cholinergic system and information processing capacity. In: Weinman J, Hunter J (eds) Memory: neurochemical and abnormal perspectives. Harwood, Glasgow, pp 87–105Google Scholar

Copyright information

© Springer-Verlag 1994

Authors and Affiliations

  • C. P. S. Smith
    • 1
  • A. J. Hunter
    • 2
  • G. W. Bennett
    • 1
  1. 1.Department of Physiology and PharmacologyMedical School, Queen's Medical CentreNottinghamUK
  2. 2.Smith Kline Beecham, Medicinal Research CentreHarlowUK

Personalised recommendations