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Research ArticleArticle

Full and Partial 5-HT1A Receptor Agonists Disrupt Learning and Performance in Rats

P. J. Winsauer, F. H. Rodriguez, A. E. Cha and J. M. Moerschbaecher
Journal of Pharmacology and Experimental Therapeutics January 1999, 288 (1) 335-347;
P. J. Winsauer
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F. H. Rodriguez
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A. E. Cha
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J. M. Moerschbaecher
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Abstract

As a means of characterizing the role of 5-hydroxytryptamine (5-HT1A) receptors in learning, a full 5-HT1Areceptor agonist, 8-hydroxy-dipropylaminotetralin (8-OH-DPAT), was administered both alone and in combination with two partial agonists (buspirone and 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl] piperazine hydrobromide (NAN-190)) and a 5-HT1A receptor antagonist (p-MPPI) to rats responding under a multiple schedule of repeated acquisition and performance of response sequences. In addition, the effects of another 5-HT1A receptor agonist, (LY228729), were also studied under this same procedure. When administered alone, both 8-OH-DPAT (0.1–3.2 mg/kg) and LY228729 (0.32–3.2 mg/kg) dose dependently decreased overall response rate and increased the percentage of errors in the acquisition and performance components. At the doses of each drug tested, both buspirone (0.32 or 1 mg/kg) and NAN-190 (1 or 3.2 mg/kg) also decreased overall response rate and increased the percentage of errors. However, the effects of these drugs differed across behavioral components and dependent measures. The effects of buspirone and NAN-190 on rate and accuracy were also different when they were administered in combination with 8-OH-DPAT. In contrast, p-MPPI (3.2 or 10 mg/kg) had little or no effect when administered alone and antagonized the effects of 8-OH-DPAT; shifting the dose-effect curves for both response rate and the percentage of errors in both components to the right. Taken together, these results indicate that complex behaviors in rats are sensitive to disruption by drugs with both full and partial 5-HT1A receptor agonist properties, and that the effects of partial 5-HT1A receptor agonists on learning may be different depending on their efficacy at pre- and postsynaptic 5-HT1A receptors.

Footnotes

  • Send reprint requests to: Dr. Peter J. Winsauer, Department of Pharmacology and Experimental Therapeutics, Louisiana State University Medical Center, 1901 Perdido Street, New Orleans, LA 70112.

  • 1 This work was supported, in part, by a grant from the National Institute on Drug Abuse (DA 04775).

  • Abbreviations:
    5-HT
    5-hydroxytryptamine
    LY228729
    (−)-4-(dipropylamino)-1,3,4,5-tetrahydrobenz-{c, d,}indole-6-carboxamide
    p-MPPI
    4-iodo-N-[2-[4-(methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinyl-benzamide hydrochloride
    NAN-190
    1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine hydrobromide
    8-OH-DPAT
    8-hydroxy-dipropylaminotetralin
    • Received September 23, 1997.
    • Accepted September 23, 1998.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 288 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 288, Issue 1
1 Jan 1999
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Research ArticleArticle

Full and Partial 5-HT1A Receptor Agonists Disrupt Learning and Performance in Rats

P. J. Winsauer, F. H. Rodriguez, A. E. Cha and J. M. Moerschbaecher
Journal of Pharmacology and Experimental Therapeutics January 1, 1999, 288 (1) 335-347;

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Research ArticleArticle

Full and Partial 5-HT1A Receptor Agonists Disrupt Learning and Performance in Rats

P. J. Winsauer, F. H. Rodriguez, A. E. Cha and J. M. Moerschbaecher
Journal of Pharmacology and Experimental Therapeutics January 1, 1999, 288 (1) 335-347;
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