Skip to main content
NCBI home page
Journal of Psychiatry & Neuroscience: JPN logoLink to Journal of Psychiatry & Neuroscience: JPN
. 1999 Mar;24(2):122–130.

Discriminative stimulus properties of indorenate, a serotonin agonist.

D N Velázquez-Martínez 1, M López Cabrera 1, H Sánchez 1, J I Ramírez 1, E Hong 1
PMCID: PMC1188992  PMID: 10212554

Abstract

OBJECTIVE: To determine whether indorenate, a serotonin-receptor agonist, can exert discriminative control over operant responses, to establish the temporal course of discriminative control and to compare its stimulus properties to a (5-HT)IA receptor agonist. [3H]-8-hydroxy-2-(di-N-propylamino) tetralin (8-OH-DPAT). DESIGN: Prospective animal study. ANIMALS: Ten male Wistar rats. INTERVENTIONS: Rats were trained to press either of 2 levers for sucrose solution according to a fixed ratio schedule, which was gradually increased. Rats were given injections of either indorenate or saline solution during discrimination training. Once they had achieved an 83% accuracy rate, rats underwent generalization tests after having received a different dose of indorenate, the training dose of indorenate at various intervals before the test, various doses of 8-OH-DPT, or NAN-190 administered before indorenate or 8-OH-DPAT. OUTCOME MEASURES: Distribution of responses between the 2 levers before the first reinforcer of the session, response rate for all the responses in the session, and a discrimination index that expressed the drug-appropriate responses as a proportion of the total responses. RESULTS: Indorenate administration resulted in discriminative control over operant responses, maintained at fixed ratio 10, at a dose of 10.0 mg/kg (but not 3.0 mg/kg). When the interval between the administration of indorenate and the start of the session was varied, the time course of its cue properties followed that of its described effects on 5-HT turnover. In generalization tests, the discrimination index was a function of the dose of indorenate employed; moreover, administration of 8-OH-DPAT (from 0.1 to 1.0 mg/kg) fully mimicked the stimulus properties of indorenate in a dose-dependent way. The (5-HT)IA antagonist NAN-190 prevented the stimulus generalization from indorenate to 8-OH-DPAT. Also, NAN-190 antagonized the stimulus control of indorenate when administered 45 minutes before the session, but not when administered 105 minutes before the session (i.e., 15 minutes before the administration of indorenate). CONCLUSION: (5-HT)IA receptors are of relevance to the stimulus function of indorenate. However, other receptor subtypes may also be involved. Hence, other agonists and specific antagonists should be studied before definite conclusions are drawn.

Full text

PDF
122

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Barrett J. E., Gleeson S. Discriminative stimulus effects of 8-OH-DPAT in pigeons: antagonism studies with the putative 5-HT1A receptor antagonists BMY 7378 and NAN-190. Eur J Pharmacol. 1992 Jul 7;217(2-3):163–171. doi: 10.1016/0014-2999(92)90841-q. [DOI] [PubMed] [Google Scholar]
  2. Barrett J. E., Vanover K. E. 5-HT receptors as targets for the development of novel anxiolytic drugs: models, mechanisms and future directions. Psychopharmacology (Berl) 1993;112(1):1–12. doi: 10.1007/BF02247357. [DOI] [PubMed] [Google Scholar]
  3. Benítez-King G., Chávez J. L., Martínez I., Antón-Tay F., Hong E. Further evidence that indorenate is a 5-HT1 agonist. Proc West Pharmacol Soc. 1991;34:433–437. [PubMed] [Google Scholar]
  4. Colpaert F. C., Koek W. Empirical evidence that the state dependence and drug discrimination paradigms can generate different outcomes. Psychopharmacology (Berl) 1995 Aug;120(3):272–279. doi: 10.1007/BF02311174. [DOI] [PubMed] [Google Scholar]
  5. Dompert W. U., Glaser T., Traber J. 3H-TVX Q 7821: identification of 5-HT1 binding sites as target for a novel putative anxiolytic. Naunyn Schmiedebergs Arch Pharmacol. 1985 Feb;328(4):467–470. doi: 10.1007/BF00692918. [DOI] [PubMed] [Google Scholar]
  6. Fernández-Guasti A., Escalante A., Hong E., Agmo A. Behavioural actions of the serotonergic anxiolytic indorenate. Pharmacol Biochem Behav. 1990 Sep;37(1):83–88. doi: 10.1016/0091-3057(90)90045-j. [DOI] [PubMed] [Google Scholar]
  7. Fernández-Guasti A., López-Rubalcava C. Evidence for the involvement of the 5-HT1A receptor in the anxiolytic action of indorenate and ipsapirone. Psychopharmacology (Berl) 1990;101(3):354–358. doi: 10.1007/BF02244053. [DOI] [PubMed] [Google Scholar]
  8. Glennon R. A. Discriminative stimulus properties of the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH DPAT). Pharmacol Biochem Behav. 1986 Jul;25(1):135–139. doi: 10.1016/0091-3057(86)90243-1. [DOI] [PubMed] [Google Scholar]
  9. Gozlan H., El Mestikawy S., Pichat L., Glowinski J., Hamon M. Identification of presynaptic serotonin autoreceptors using a new ligand: 3H-PAT. Nature. 1983 Sep 8;305(5930):140–142. doi: 10.1038/305140a0. [DOI] [PubMed] [Google Scholar]
  10. Hong E., Villalon C. M. External carotid vasodilation induced by serotonin and indorenate. Proc West Pharmacol Soc. 1988;31:99–101. [PubMed] [Google Scholar]
  11. Hoyer D., Clarke D. E., Fozard J. R., Hartig P. R., Martin G. R., Mylecharane E. J., Saxena P. R., Humphrey P. P. International Union of Pharmacology classification of receptors for 5-hydroxytryptamine (Serotonin). Pharmacol Rev. 1994 Jun;46(2):157–203. [PubMed] [Google Scholar]
  12. Hoyer D., Engel G., Kalkman H. O. Molecular pharmacology of 5-HT1 and 5-HT2 recognition sites in rat and pig brain membranes: radioligand binding studies with [3H]5-HT, [3H]8-OH-DPAT, (-)[125I]iodocyanopindolol, [3H]mesulergine and [3H]ketanserin. Eur J Pharmacol. 1985 Nov 26;118(1-2):13–23. doi: 10.1016/0014-2999(85)90658-2. [DOI] [PubMed] [Google Scholar]
  13. Lucki I. Rapid discrimination of the stimulus properties of 5-hydroxytryptamine agonists using conditioned taste aversion. J Pharmacol Exp Ther. 1988 Dec;247(3):1120–1127. [PubMed] [Google Scholar]
  14. López Cabrera M., Velázquez Martínez D. N., Prado R., García G., Ortiz R. Effects of the intracerebroventricular administration of indorenate and fenfluramine on spontaneous behavior and food intake in rats. Proc West Pharmacol Soc. 1991;34:465–468. [PubMed] [Google Scholar]
  15. Mansbach R. S., Barrett J. E. Discriminative stimulus properties of buspirone in the pigeon. J Pharmacol Exp Ther. 1987 Feb;240(2):364–369. [PubMed] [Google Scholar]
  16. Rabin R. A., Winter J. C. Studies of the biochemical basis for the discriminative properties of 8-hydroxy-2-(di-n-propylamino)tetralin. Eur J Pharmacol. 1993 Apr 28;235(2-3):237–243. doi: 10.1016/0014-2999(93)90142-5. [DOI] [PubMed] [Google Scholar]
  17. Tricklebank M. D., Neill J., Kidd E. J., Fozard J. R. Mediation of the discriminative stimulus properties of 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) by the putative 5-HT1A receptor. Eur J Pharmacol. 1987 Jan 6;133(1):47–56. doi: 10.1016/0014-2999(87)90204-4. [DOI] [PubMed] [Google Scholar]
  18. Winter J. C., Rabin R. A. Yohimbine as a serotonergic agent: evidence from receptor binding and drug discrimination. J Pharmacol Exp Ther. 1992 Nov;263(2):682–689. [PubMed] [Google Scholar]

Articles from Journal of Psychiatry and Neuroscience are provided here courtesy of Canadian Science Publishing

RESOURCES