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Role of Somatodendritic and Postsynaptic 5-HT1A Receptors on Learning and Memory Functions in Rats

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Abstract

Memory impairment is a major problem afflicting mankind. The association between memory functions and neurotransmitter functions is of great interest for understanding brain function. Serotonergic pathways play an important role in the modulation of memory functions but the importance of its receptor types and subtypes on memory functions is still unclear. Activation and blockade of various serotonin (5-HT) receptors has been reported to alter cognitive processes and 5-HT receptor antagonism could be beneficial in the treatment of cognitive diseases. The role of 5-HT on memory functions is complicated. Among the 5-HT receptors subtypes, 5-HT1A receptors are of special interest because these receptors are present in the brain areas involved in learning and memory functions such as hippocampus and cortex. The present study was therefore designed to investigate the effect of activation and blockade of somatodendritic and/or postsynaptic 5-HT1A receptor on learning and memory functions in rats using modified version of water maze. In this study, 8-OH-DPAT (8-hydroxy-2-(di-N-propylamino) tetralin) at 0.3 mg/kg significantly enhanced learning acquisition (LA), short-term memory (STM) and long term memory (LTM) of rats pre-injected with saline suggesting that the activation of pre-synaptic 5-HT1A receptors by its agonist enhanced the memory functions of rats. Conversely, rats injected with 8-OH-DPAT at 1.0 mg/kg exhibited impaired LA and STM and had no effect on LTM. It was also shown in this study that blockade of 5-HT1A receptors by spiperone enhanced LA, had no effect on STM but impaired the LTM, which showed that the blockade of 5-HT1A receptors by its antagonist exerts different effect on different types of memory. This study suggests that 5-HT1A receptor could be used as a significant pharmacological target for the treatment of CNS diseases. Unraveling the role of serotonin in cognition and memory disorders could provide better therapy and it may lead to new insights in our understandings of learning and memory.

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References

  1. Khaliq S, Haider S, Ahmed SP, Perveen T, Haleem DJ (2006) Relationship of brain tryptophan and serotonin in improving cognitive performance in rats. Pak J Pharm Sci 19:11–15

    PubMed  CAS  Google Scholar 

  2. Haider S, Khaliq S, Ahmed SP, Haleem DJ (2006) Long term tryptophan administration enhances cognitive performances and increases 5HT metabolism in the hippocampus of female rats. Amino Acids 31:421–425

    Article  PubMed  CAS  Google Scholar 

  3. Haider S, Shameem S, Ahmed SP, Perveen T, Haleem DJ (2005) Repeated administration of lead decreased brain 5HT metabolism and produces memory deficits in rats. CMBL 10:669–676

    PubMed  CAS  Google Scholar 

  4. Ogren SO, Eriksson TM, Elvander-Tottie E, D’Addario C, Ekstrom JC, Svenningsson P, Meister B, Kehr J, Stiedl O (2008) The role of 5-HT1A receptors in learning and memory. Behav Brain Res 195:54–77

    Article  PubMed  Google Scholar 

  5. Hoyer D, Clarke DE, Fozard JR, Hartig PR, Martin GR, Mylecharane EJ, Saxena PR, Humphrey PP (1994) International Union of Pharmacology classification of receptors for 5-hydroxytryptamine (serotonin). Pharmacol Rev 46:157–203

    PubMed  CAS  Google Scholar 

  6. Jeltsch H, Bertrand F, Galani R, Lazarus C, Schimchowitsch S, Cassel JC (2004) Intraseptal injection of the 5-HT1A/5-HT7 agonist 8-OH-DPAT and working memory in rats. Psychopharmacol (Berl) 175:37–46

    Google Scholar 

  7. Pazos A, Palacios JM (1985) Quantitative autoradiographic mapping of serotonin receptors in the rat brain. I. Serotonin 1 receptors. Brain Res 346:205–230

    Article  PubMed  CAS  Google Scholar 

  8. Chalmers DT, Watson SJ (1991) Comparative anatomical distribution of 5-HT1A receptor mRNA and 5-HT1A binding in rat brain: a combined in situ hybridisation/in vitro receptor autoradiographic study. Brain Res 561:51–60

    Article  PubMed  CAS  Google Scholar 

  9. Pompeiano M, Palacios JM, Mengod G (1992) Distribution and cellular localization of mRNA coding for 5-HT1A receptor in the rat brain: correlation with receptor binding. J Neurosci 12:440–453

    PubMed  CAS  Google Scholar 

  10. Verge D, Daval G, Patey A, Gozlan H, el Mestikawy S, Hamon M (1985) Presynaptic 5-HT autoreceptors on serotonergic cell bodies and/or dendrites but not terminals are of the 5-HT1A subtype. Eur J Pharmacol 113:463–464

    Article  PubMed  CAS  Google Scholar 

  11. Sprouse JS, Aghajanian GK (1986) (-)-Propranolol blocks the inhibition of serotonergic dorsal raphe cell firing by 5-HT1A selective agonists. Eur J Pharmacol 128:295–298

    Article  PubMed  CAS  Google Scholar 

  12. Sprouse JS, Aghajanian GK (1986) Responses of hippocampal pyramidal cells to putative serotonin 5-HT1A and 5-HT1B agonists: a comparative study with dorsal raphe neurons. Neuropharmacology 27:707–715

    Article  Google Scholar 

  13. Sharp T, Bramwell SR, Hjorth S, Grahame-Smith DG (1989) Pharmacological characterization of 8-OH-DPAT-induced inhibition of rat hippocampal 5-HT release in vivo as measured by microdialysis. Br J Pharmacol 98:989–997

    Article  PubMed  CAS  Google Scholar 

  14. Luttgen M, Ogren SO, Meister B (2005) 5-HT1A receptor mRNA and immunoreactivity in the rat medial septum/diagonal band of Broca-relationships to GABAergic and cholinergic neurons. J Chem Neuroanat 29:93–111

    Article  PubMed  CAS  Google Scholar 

  15. Madjid N, Tottie EE, Luttgen M, Meister B, Sandin J, Kuzmin A, Stiedl O, Ogren SO (2006) 5-Hydroxytryptamine 1A receptor blockade facilitates aversive learning in mice: interactions with cholinergic and gutamatergic mechanism. J Pharmacol Exp Ther 316:581–591

    Article  PubMed  CAS  Google Scholar 

  16. Elvander-Tottie E, Eriksson TM, Sandin J, Ogren SO (2009) 5-HT1A and NMDA receptors interact in the rat medial septum and modulate hippocampal dependent spatial learning. Hippocampus 19:1187–1198

    Article  PubMed  CAS  Google Scholar 

  17. Meneses A (2003) A pharmacological analysis of an associative learning task: 5-HT1 to 5-HT7 receptor subtypes function on a pavlovian/instrumental auto shaped memory. Learn Mem 10:363–372

    Article  PubMed  Google Scholar 

  18. Buhot MC, Wolff M, Benhassine N, Costet P, Hen R, Segu L (2003) Spatial learning in the 5-HT1B receptor knockout mouse: selective facilitation/impairment depending on the cognitive demand. Learn Mem 10:466–477

    Article  PubMed  Google Scholar 

  19. Petkov VD, Kehayov R (1994) Effects of agonists and antagonists of some serotonin-receptor subtypes on memory and their modulation by the 5-HT uptake inhibitor fluoxetine. Acta Physiol Pharmacol Bulg 20:83–90

    PubMed  CAS  Google Scholar 

  20. Petkov VD, Belcheva S, Konstantinova E, Kehayov R (1995) Participation of different 5-HT receptors in the memory process in rats and its modulation by the serotonin depletor p-chlorophenylalanine. Acta Neurobiol Exp (Wars) 55:243–252

    CAS  Google Scholar 

  21. Manuel-Apolinar Meneses (2004) 8-OH-DPAT facilitated memory consolidation and increased hippocampal and cortical cAMP production. Behav Brain Res 148:179–184

    Article  PubMed  CAS  Google Scholar 

  22. Carli M, Samanin R (1992) 8-Hydroxy-2-(di-n-propylamino)tetralin impairs spatial learning in a water maze: role of postsynaptic 5-HT1A receptors. Br J Pharmacol 105:720–726

    Article  PubMed  CAS  Google Scholar 

  23. Lee EH, Lin WR, Chen HY, Shiu WH, Liang KC (1992) Fluoxetine and 8-OH-DPAT in the lateral septum enhances and impairs retention of an inhibitory avoidance response in rats. Physiol Behav 51:681–688

    Article  PubMed  CAS  Google Scholar 

  24. Otano A, Garcia-Osta A, Ballaz S, Frechilla D, Del Rio J (1999) Facilitation by 8-OH-DPAT of passive avoidance performance in rats after inactivation of 5-HT1A receptors. Br J Pharmacol 128:1691–1698

    Article  PubMed  CAS  Google Scholar 

  25. Misane I, Ögren SO (2000) Multiple 5-HT receptors in passive avoidance: comparative studies of p-chloroamphetamine and 8-OH-DPAT. Neuropsychopharmacology 22:168–190

    Article  PubMed  CAS  Google Scholar 

  26. Egashira N, Yano A, Ishigami N, Mishima K, Iwasaki K, Fujioka M, Matsushita M, Nishimura R, Fujiwara M (2006) Investigation of mechanisms mediating 8-OH-DPAT induced impairment of spatial memory: involvement of 5-HT1A receptors in the dorsal hippocampus in rats. Brain Res 1069:54–62

    Article  PubMed  CAS  Google Scholar 

  27. Misane I, Johansson C, Ögren SO (1998) Analysis of the 5-HT1A receptor involvement in passive avoidance in the rat. Br J Pharmacol 125:499–509

    Article  PubMed  CAS  Google Scholar 

  28. Carli M, Luschi R, Garofalo P, Samanin R (1995) 8-OH-DPAT impairs spatial but not visual learning in a water maze by stimulating 5-HT1A receptors in the hippocampus. Behav Brain Res 67:67–74

    Article  PubMed  CAS  Google Scholar 

  29. Misane I, Ögren SO (2003) Selective 5-HT1A antagonists WAY 100635 and NAD-299 attenuate the impairment of passive avoidance caused by scopolamine in the rat. Neuropsychopharmacology 28:253–264

    Article  PubMed  CAS  Google Scholar 

  30. Plech A, Klimkiewiez T, Jakrzewska H (2000) Neurotoxic effect of copper salts in rats. Pol J Environ Stud 9:301–304

    CAS  Google Scholar 

  31. Haider S, Khaliq S, Haleem DJ (2007) Enhanced serotonergic neurotransmission in the hippocampus following tryptophan administration improves learning acquisition and memory consolidation in rats. Pharmacol Rep 59:53–57

    PubMed  CAS  Google Scholar 

  32. Haleem DJ, Kennett GA, Curzon G (1990) Hippocampal 5-HT syntheses are greater in females than in males and are more decreased by 5HT1A agonist 8-OH-DPAT. J Neural Transm 79:93–101

    Article  CAS  Google Scholar 

  33. Haleem DJ (1992) Sex differences in neurochemical and behavioral effects of 8-OH-DPAT. Life Sci 50:221–226

    Article  Google Scholar 

  34. Haleem DJ, Naz H, Perveen T, Haider S, Ahmed SP, Khan NH (2002) Serotonin and serotonin 1A receptors in the failure of ethanol treated rats to adapt to a repeated stress schedule. J Stud Alcohol 63:389–396

    PubMed  Google Scholar 

  35. Schiapparelli L, Del Rio J, Frechilla D (2005) Serotonin 5-HT receptor blockade enhances Ca2+/calmodulin-dependent protein kinase II function and membrane expression of AMPA receptor subunits in the rat hippocampus: implications for memory formation. J Neurochem 94:884–895

    Article  PubMed  CAS  Google Scholar 

  36. Steckler T, Sahgal A (1995) How do glutamateric drugs affect cognitive function? Commentary on Danysz et al., ‘modulation of learning processes by ionotropic glutamate receptor ligands’. Behav Pharmacol 6:475–477

    Article  PubMed  CAS  Google Scholar 

  37. Steckler T, Sahgal A (1995) The role of serotonergic-cholinergic interactions in the mediation of cognitive behaviour. Behav Brain Res 67:165–199

    Article  PubMed  CAS  Google Scholar 

  38. Jeltsch-David H, Koenig J, Cassel JC (2008) Modulation of cholinergic functions by serotonin and possible implications in memory: general data and focus on 5-HT1A receptors of the medial septum. Behav Brain Res 195:86–97

    Article  PubMed  CAS  Google Scholar 

  39. Lejeune F, Millan MJ (1998) Induction of burst firing in ventral tegmental area dopaminergic neurons by activation of serotonin 5-HT1A receptors: WAY100635-reversible actions of the highly selective ligands, flesinoxan and S15535. Synapse 30:172–180

    Article  PubMed  CAS  Google Scholar 

  40. Gronier B (2008) Involvement of glutamate neurotransmission and N-methyl-d-aspartate receptor in the activation of midbrain dopamine neurons by 5-HT1A receptor agonist: an electrophysiological study in the rat. Neuroscience 156:995–1004

    Article  PubMed  CAS  Google Scholar 

  41. Meneses A, Perez-Garcia G (2007) 5-HT1A receptors and memory. Neurosci Biobehav Rev 31:705–727

    Article  PubMed  CAS  Google Scholar 

  42. Bianchi C, Siniscalchi A, Beani L (1990) 5-HT1A agonists increase and 5-HT3 agonists decrease acetylcholine efflux from the cerebral cortex of freely-moving guinea-pigs. Br J Pharmacol 101:448–452

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Biochemistry, Neurochemistry and Biochemical Neuropharmacology Research Unit, University of Karachi, Karachi, Pakistan

    Saida Haider, Saiqa Tabassum & Darakhshan J. Haleem

  2. Department of Biochemistry, Federal Urdu University, Karachi, Pakistan

    Saima Khaliq

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  1. Saida Haider
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  2. Saima Khaliq
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  3. Saiqa Tabassum
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  4. Darakhshan J. Haleem
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Correspondence to Saida Haider.

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Haider, S., Khaliq, S., Tabassum, S. et al. Role of Somatodendritic and Postsynaptic 5-HT1A Receptors on Learning and Memory Functions in Rats. Neurochem Res 37, 2161–2166 (2012). https://doi.org/10.1007/s11064-012-0839-5

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  • DOI: https://doi.org/10.1007/s11064-012-0839-5

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