Skip to main content
Log in

Role of serotonin in memory: facilitation by alaproclate and zimeldine

  • Original Investigations
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

The effects of alaproclate and zimeldine on memory retrieval were examined in male Swiss Webster mice using a one-trial inhibitory avoidance task. All drugs were administered IP prior to the retention test 24 h after training. Both drugs were found to facilitate memory retrieval significantly in a dose-and time-dependent fashion that could not be explained in terms of non-specific effects of the drug (illness, lack of motility, etc.) at the time of the test. The temporal effects of alaproclate and zimeldine on memory closely followed their course of concentration of the drug within the blood stream. The facilitation of retrieval induced by alaproclate and zimeldine was blocked by the putative serotonergic receptor agonist quipazine but not blocked by the antagonist cyproheptadine. Pretreatment with quipazine alone in a group of animals trained to a shock level which normally results in high levels of suppression was not sufficient to produce memory impairment, suggesting that quipazine was probably antagonizing the facilitative effects of alaproclate and zimeldine directly, rather than overriding the facilitation through an indirect action on retrieval in general. The present results lend further support to the suggestion that serotonin plays a significant role in memory.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Aghajanian GK, Haigler HJ, Bennett JL (1975) Amine receptors in CNS. III. 5-hydroxytryptamine in brain. In: Iversen LL, Iversen SD, Snyder SH (eds) Handbook of psychopharmacology, vol. 6. Plenum Press, New York, pp 63–96

    Google Scholar 

  • Carlsson A, Jonason J, Lindquvist M, Fuxe K (1969) Demonstration of extraneuronal 5-hydroxytryptamine accumulation in brain following membrane-pump blockade by chlorimipramine. Brain Res 12:456–460

    Google Scholar 

  • Corrodi H, Fuxe K (1968) The effect of imipramine on central monoamine neurons. J Pharm Pharmacol 20:230–231

    Google Scholar 

  • Essman WG (1970) Some neurochemical correlates of altered memory consolidation. Trans NY Acad Sci 32:948–973

    Google Scholar 

  • Farnebo L-O, Hamberger B (1974) Regulation of 3H-5-hydroxytryptamine release from rat brain slices. J Pharm Pharmacol 26:642–644

    Google Scholar 

  • Graeff FG, Schoenfeld RI (1970) Tryptaminergic mechanisms in punished and nonpunished behaviour. J Pharmacol Exp Ther 173:277–283

    Google Scholar 

  • Graffner C, Nicklasson M, Lindgren JE (1984) Correlations between in vitro dissolution rate and biovasilability of alaproclate tablets. J Pharmacokinet Biopharmacol (in press)

  • Green AR, Youdim MBH, Grahame-Smith WG (1976) Quipazine: its effects on rat brain 5-hydroxytryptamine metabolism, monoamine oxidase activity and behaviour. Neuropharmacology 15:173–179

    Google Scholar 

  • Haigler HJ, Aghajanian GK (1974) Peripheral serotonin antagonists: failure to antagonize serotonin in brain areas receiving a prominent serotonergic input. J Neuronal Transm 35:257–273

    Google Scholar 

  • Hall H, Ögren SO (1981) Effects of antidepressant drugs on different receptors in the brain. Eur J Pharmacol 70:393–407

    Google Scholar 

  • Hamon M, Bourgoin S, Enjialbert A, Bockaert J, Hery F, Ternaux JP, Glowinski J (1976) The effects of quipazine on 5-HT metabolism in the rat brain. Naunyn-Schmiederbergs Arch Pharmacol 294:99–108

    Google Scholar 

  • Hamon M, Nelson DL, Herbet A, Glowinski J (1980) Multiple receptors for serotonin in rat brain. In: Pepeu G, Kuhar MJ, Enna SJ (eds). Receptors for neurotransmitters and peptide hormones. Raven Press, New York, pp 223–233

    Google Scholar 

  • Hunter B, Zornetzer SF, Jarvik ME, McGaugh JL (1977) Modulation of learning and memory: Effects of drugs influencing neurotransmitters. In: Iversen LL, Iversen SD, Snyder SH (eds), Handbook of psychopharmacology, vol. 8. Plenum Press, New York, pp 531–577

    Google Scholar 

  • Jacoby JH, Howd RA, Levin MS, Wurtman RJ (1976) Mechanisms by which quipazine, a putative serotonin receptor agonist, alters brain 5-hydroxyindole metabolism. Neuropharmacology 15:529–534

    Google Scholar 

  • Landsdown MJR, Nash HL, Preston PR, Wallis DI, Williams RG (1980) Antagonism of 5-hydroxytryptamine receptors by quipazine. Br J Pharmacol 68:525–532

    Google Scholar 

  • Lindberg UH, Thorberg SO, Bentsson S, Renyi AL, Roos SB, Ogren SO (1978) Inhibitors of neuronal monoamine uptake. 2. Selective inhibition of 5-hydroxytryptamine uptake by amino acid esters of phenethyl alcohols. J Med Chem 21:448–456

    Google Scholar 

  • Lorens SA (1978) Some behavioural effects of serotonin depletion depend on method: A comparison of 5,7-dihydroxytryptamine, p-chlorophenylalanine, p-chloroamphetamine and electrolytic raphe lesions. Am NY Acad Sci 305:532–555

    Google Scholar 

  • Martin LL, Sanders-Bush E (1982) The serotonin autoreceptor. Antagonism by quipazine. Neuropharmacology 21:445–450

    Google Scholar 

  • McCall RB, Aghajanian GK (1980) Pharmacological characterization of serotonin receptors in the facial motor nucleus: A microiontophoretic study 65:175–183

    Google Scholar 

  • Ogren SO (1982) Central serotonin neurones and learnin gin the rat. In: Osborne NN (ed): Biology of serotonergic transmision. John Wiley & Sons, London, pp 317–334

    Google Scholar 

  • Ogren SO, Ross SB, Holm AC, Baumann L (1977) 5-Hydroxytryptamine and avoidance performance in the rat. Antagonism of the acute effect of p-chloroamphetamine by zimelidine, and inhibitor of 5-hydroxytryptamine uptake. Neurosci Lett 7:331–336

    Google Scholar 

  • Ögren SO, Fuxe K, Agnati LF, Gustavsson JÅ, Jonsson G, Holm AC (1979) Re-evaluation of the indoleamine hypothesis of depression. Evidence for a reduction of functional activity of central 5-HT systems by antidepressant drugs. J Neural Transm 46:85–103

    Google Scholar 

  • Ögren SO, Fuxe K, Archer T, Hall H, Holm AC, Köhler C (1981a) Studies on the role of central 5-HT neurons in avoidance learning: A behavioural and biochemical analysis. In: Haber B, Gabay S, Issidorides MR, Alivisatos SGA (eds) Serotonin: Current aspects of neurochemistry and function. Plenum Press, New York, pp 681–705

    Google Scholar 

  • Ögren SO, Cott JM, Hall H (1981b) Sedative/anxiolytic effects of antidepressants in animals. Acta Psychiatr Scand 63:277–288

    Google Scholar 

  • Ögren SO, Holm AC, Hall H, Lindberg UH (1984) Alaproclate, a new selective 5-HT uptake inhibitor with therapeutic potential in depression and senile dementia. J Neural Transm 59:265–288

    Google Scholar 

  • Peroutka SJ, Lebowitz RM, Snyder SH (1918) Two distinct central serotonin receptors with different physiological functions. Science 212:827–829

    Google Scholar 

  • Ross SB, Ögren SO, Renyi AL (1976) (Z)-Dimethylamino-1-(4-bromophenyl)-1-(3-pyridyl)propene (H102/09), a new selective inhibitor of the neuronal 5-hydroxytryptamine uptake. Acta Pharmacol Toxicol 39:152–166

    Google Scholar 

  • Ross SB (1982) The characteristics of serotonin uptake systems. In: Osborne NN (ed) Biology of serotonergic transmission. John Whiley & Sons, London, pp 159–195

    Google Scholar 

  • Ross SB, Renyi AL (1977) Inhibition of the neuronal uptake of 5-hydroxytryptamine and noradrenaline in rat brain by (Z)-and (E)-3-(4-bromophenyl)-N,N-dimethyl-3-(3-pyridyl)allylamines and their secondary analogues. Neuropharmacology 16:57–63

    Google Scholar 

  • Westerlund D, Nilsson LB, Jaksen Y (1979) Straight-phase ion-pair chromatography of zimeldine and similar divalent amines. J Liquid Chromatogr 2:373–405

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Altman, H.J., Nordy, D.A. & Ögren, S.O. Role of serotonin in memory: facilitation by alaproclate and zimeldine. Psychopharmacology 84, 496–502 (1984). https://doi.org/10.1007/BF00431456

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00431456

Key words

Navigation