Psychopharmacology

, Volume 100, Issue 1, pp 49–53 | Cite as

Effects of carbamazepine on 5-hydroxytryptamine function in rodents

  • M. Elphick
  • S. M. P. Anderson
  • K. F. Hallis
  • D. G. Grahame-Smith
Original Investigations

Abstract

The effects of carbamazepine (CBZ) on brain 5-hydroxytryptamine (5-HT) function were investigated in rodents pretreated with CBZ acutely or for 14 days. In behavioural experiments, mice pretreated with 14 days CBZ showed increased 5-HT2-mediated head twitch behaviour after injection of carbidopa (25 mg/kg) followed by 5-hydroxytryptophan (5-HTP, 100 mg/kg). However, no change in head twitches after 5-methoxy,N,N,-dimethyltryptamine (5MeODMT 5.0 mg/kg), a direct agonist, was observed. Chronic CBZ administration to rats did not alter either the behavioural syndrome induced by 8-hydroxy-2-dipropy-laminotetralin (8-OH-DPAT, 1.0 mg/kg), an index of post-synaptic 5-HT1A responses, or hypothermia after 8-OH-DPAT (0.5 mg/kg) which is thought to reflect presynaptic 5-HT1A activity. Both hyperactivity and the behavioural syndrome seen after tranylcypromine (20 mg/kg) followed byl-tryptophan (100 mg/kg) were decreased by prior treatment with CBZ (14 days). Accumulation of 5-HTP after administration of the amino acid decarboxylase inhibitor NSD1015 (100 mg/kg) was decreased after acute CBZ (50 mg/kg) in hippocampus. However, after 14 days oral treatment no change in this measure of 5-HT synthesis was seen, in either hippocampus or frontal cortex.

CBZ (50 µM) added to superfused brain slices did not affect potassium-stimulated [3H]-5-HT release. However, hippocampal slices from rats pretreated with CBZ (14 days) showed increased potassium-stimulated [3H]-5-HT release. CBZ (14 days) did not alter 5-HT2 binding in rat frontal cortex. These results indicate a depressant effect of acute CBZ upon presynaptic 5-HT activity and an increase in presynaptic 5-HT function when CBZ is given for 14 days. Post-synaptic 5-HT function was, however, not altered by CBZ.

Key words

Carbamazepine 5-HT Behaviour Synthesis Release Binding 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Carlsson A, Lindqvist M (1973) In vivo measurements of tryptophan and tyrosine hydroxylase activities in mouse brain. J Neural Transm 34:79–91PubMedCrossRefGoogle Scholar
  2. Elphick M (1988) The chmcal uses and pharmacology of carbamazepine in psychiatry. Int Clin Psychopharmacol 3:185–203PubMedCrossRefGoogle Scholar
  3. Elphick M (1989) The effects of carbamazepine on dopamine function. PsychopharmacologyGoogle Scholar
  4. Elphick M, Taghavi Z, Powell T, Godfrey PP (1988) Carbamazepine treatment does not alter agonist-stimulated inositol phospholipid turnover in rat cortex: a comparison with lithium. Eur J Pharmacol 3:411–414CrossRefGoogle Scholar
  5. Goodwin GM, De Souza RJ, Green AR (1985) The pharmacology of the hypothermic response in mice to 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT). A model of presynaptic 5-HT1 function. Neuropharmacology 24:1187–1194PubMedCrossRefGoogle Scholar
  6. Goodwin GM, De Souza RJ, Wood AR, Green AR (1986) The enhancement by lithium of the 5-HT1A mediated serotonin syndrome produced by 8-OH-DPAT in the rat: evidence for a postsynaptic mechanism. Psychopharmacology 90:488–493PubMedGoogle Scholar
  7. Grahame-Smith DG (1967) The biosynthesis of 5-hydroxytrypta-mine in brain. Biochem J 105:351–361PubMedGoogle Scholar
  8. Grahame-Smith DG (1971) Studies in vivo on the relationship between brain tryptophan brain 5-HT synthesis and hyperactivity in rats treated with monoamine oxidase inhibitor andl-tryptophan. J Neurochem 18:1053–1066PubMedCrossRefGoogle Scholar
  9. Green AR, Grahame-Smith DG (1974) The role of brain dopamine in the hyperactivity syndrome produced by increased 5-hydroxytryptamine synthesis in rats. Neuropharmacology 13:949–959PubMedCrossRefGoogle Scholar
  10. Green AR, Johnson P, Mountford JA, Nimgaonkar VL (1983) Antidepressant treatment: effects in rodents on dose-response curves of 5-hydroxytryptamine- and dopamine-mediated behaviours and 5-HT2 receptor number in frontal cortex. Br J Pharmacol 8:377–385Google Scholar
  11. Green AR, Johnson P, Mountford JA, Nimgaonkar VL (1985) Some anticonvulsant drugs alter monoamine-mediated behaviour in mice in ways similar to electroconvulsive shock, implications for antidepressant therapy. Br J Pharmacol 84:337–346PubMedGoogle Scholar
  12. Lane JD, Aprison MH (1978) The flux of radio label through components of the serotonergic system following the injection of [3H]-tryptophan: product-precursor anomilies providing evidence that serotonin exists in multiple pools. J Neurochem 30:671–678PubMedCrossRefGoogle Scholar
  13. Metz A, Goodwin GM, Green AR (1985) The administration of baclofen to mice increases 5-HT2-mediated head-twitch behaviour and 5-HT2 receptor number in frontal cortex. Neuropharmacology 24 (4):367–360CrossRefGoogle Scholar
  14. Molliver M (1987) Serotonergic neuronal systems: what their anatomic organisation tells us about function. J Clin Pharmacol [Suppl 6] 7:35–235Google Scholar
  15. Post RM, Uhde TW (1986) Anticonvulsants in non-epileptic psychosis. In: Trimble MR, Bolwig TG (eds) Aspects of epilepsy and psychiatry. Wiley, Chichester, pp 177–212Google Scholar
  16. Pratt JA, Jenner P, Marsden CD (1985) Comparison of the effects of benzodiazepines and other anticonvulsant drugs on synthesis and utilisation of 5-HT in mouse brain: Neuropharmacology 24 (1):59–68PubMedCrossRefGoogle Scholar
  17. Smith DF (1983) Lithium and carbamazepine: effects on learned taste aversion and open field behaviour in rats. Pharmacol Biochem Behav 18:483–488PubMedCrossRefGoogle Scholar
  18. Wood AJ, Goodwin GM (1987) A review of the biochemical and neuropharmacological actions of lithium. Psychol Med 17:579–600PubMedCrossRefGoogle Scholar
  19. Zaroslinski JF, Browne RK, Possley LH (1971) Propylene glycol as a drug solvent in pharmacologic studies. Toxicol Appl Pharmacol 19:573–578PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 1990

Authors and Affiliations

  • M. Elphick
    • 1
  • S. M. P. Anderson
    • 1
  • K. F. Hallis
    • 1
  • D. G. Grahame-Smith
    • 1
  1. 1.MRC Unit and University Department of Clinical Pharmacology, Radcliffe InfirmaryOxfordUK

Personalised recommendations