Regular Article
5-HT1AReceptors Modulate the Consolidation of Learning in Normal and Cognitively Impaired Rats,☆☆,

https://doi.org/10.1006/nlme.1998.3866Get rights and content

Abstract

Attempts were made to further analyze the role of 5-HT1Areceptors in consolidation of learning by evaluating the role of these receptors in cognitively normal and impaired animals. The effects of post-training administration of 8-OH-DPAT and 5-HT1Areceptor antagonists, WAY 100135, WAY 100635, and S-UH-301, plus the cholinergic and glutamatergic antagonists, scopolamine and dizolcipine, respectively, were determined using an autoshaping learning task. The results showed that 8-OH-DPAT increased the number of conditioned responses, whereas WAY100135, WAY100635, and S-UH-301, and the 5-HT depleter,p-chloroamphetamine (PCA), had no effect. PCA did not change the silent properties of the 5-HT1Areceptor antagonists. PCA, WAY100635, and S-UH-301, but not GR127935 (a 5-HT1B/1D-receptor antagonist) or MDL100907 (a 5-HT2Areceptor antagonist), reversed the effect to 8-OH-DPAT. Ketanserin (a 5-HT2A/2Creceptor antagonist) and ondansetron (a 5-HT3receptor antagonist), at a dose that increased the conditioned responses by itself, reversed the effect of 8-OH-DPAT. Moreover, 8-OH-DPAT or S-UH-301 reversed the learning deficit induced by scopolamine and dizocilpine whereas WAY100635 reversed the effect of scopolamine only. These data confirm a role for presynaptic 5-HT1Areceptors during the consolidation of learning and support the hypothesis that serotonergic, cholinergic, and glutamatergic systems interact in cognitively impaired animals.

References (49)

  • J.L. McGaugh

    Dissociating learning and performance: Drug and hormone enhancement of memory storage

    Brain Research Bulletin

    (1989)
  • A. Meneses et al.

    Modification of 8-OH-DPAT effect on learning by manipulation of the assay conditions

    Behavioral Neural Biology

    (1994)
  • A. Meneses et al.

    Mechanisms of action of 8-OH-DPAT on learning and memory

    Pharmacology Biochemistry Behavior

    (1994)
  • A. Meneses et al.

    A pharmacological analysis of serotonergic receptors: Effects of their activation or blockade in learning

    Progress in Neuro-Psychopharmacology and Biological Psychiatry

    (1997)
  • B.S. O'Dowd et al.

    Chicks injected with antisera to either S-100α or S-100β protein develop amnesia for a passive avoidance task

    Neurobiology of Learning and Memory

    (1997)
  • P. Riekkinen

    5-HT1A

    European Journal of Pharmacology

    (1994)
  • M. Riekkinen et al.

    Interaction between 5-HT(1A)

    Brain Research

    (1994)
  • J. Sirviö et al.

    Experimental studies on the role of serotonin in cognition

    Progress in Neurobiology

    (1994)
  • J.Y. Zhang et al.

    Serotonin3

    Neuropharmacology

    (1994)
  • G.K. Aghajanian

    Electrophysiology of serotonin receptor subtypes and signal transduction pathways

    Psychopharmacology: The fourth generation of progress

    (1995)
  • R. Andrade

    Electrophysiology of 5-HT1A

    Drug Development Research

    (1992)
  • Azmitia, E. C. Whitaker-Azmitia, P. M. 1995, Anatomy, cell biology, and plasticity of serotonergic system, In, E. F....
  • A.C. Bartolomeo et al.

    Attenuated MK-801-induced impairment of radial maze performance in rats: A possible model predicting efficacy in Alzheimer's disease

    Society of Neuroscience Abstract

    (1996)
  • P. Blier et al.

    Differential properties of pre- and postsynaptic 5-hydroxytryptamine1A receptors in the dorsal raphe and hippocampus. 1. Effect of spiperone

    Journal of Pharmacology Experimental Therapeutic

    (1993)
  • Cited by (0)

    The authors thank the pharmaceutical companies for their generous gifts (see the Drugs section). This work was written while A.M. was a Pan American–CONACYT Fellow at the Gerontology Research Center, National Institute on Aging, in Baltimore, MD. The authors thank Edward L. Spangler for critically reading the manuscript.

    ☆☆

    Correspondence and reprint requests should be addressed to Alfredo Meneses, Terapéutica Experimental, Departomento de Farmacologı́a y Toxicologı́a, CINVESTAV-IPN, Apartado Postal 22026, México, D.F., 14000, México.

    E. F. BloomD. J. Kupfer

    View full text