Discriminative stimulus properties of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OHDPAT)

implications for understanding the actions of novel anxiolytics

Kathryn Cunningham, Patrick M. Callahan, James B. Appel

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

8-Hydroxy-2-(di-n-propylamino)tetralin (8-OHDPAT) has effects both characteristic of a serotonin (5-hydroxyytryptamine; 5-HT) agonist and antagonist. To investigate the mechanism(s) of action 8-OHDPAT in vivo, rats were trained to discrimate 8-OHDPAT (0.4 mg/kg) from saline and given various neuroactive compounds during substitution test sessions. Of the 5-HT agonists tested, d-lysergic acid diethylamide, 5-methoxy-n,n-dimethyltryptamine, quipazine, Ru 24969 and 1-(m-trifluoromethylphenyl) piperazine did not mimic the training drug; the dopamine agonists apomorphine and SKF 38393 as well as the α2-adrenoceptor agonist clonidine engendered predominantly saline-lever responding. However, the novel anxiolytics buspirone and ipsapirone as well as the ergot derivative lisuride substituted completely for 8-OHDPAT. In combination tests, 5-HT (ketanserin, metergoline, methysergide, pirenperone), dopamine (haloperidol) and norepinephrine antagonists (prazosin, propranolol) failed to attenuate the 8-OHDPAT cue. The similar stimulus properties of 8-OHDPAT and the novel anxiolytics (buspirone, ipssapirone) are mirrored by the common abilities of these agents to selectively inhibit 5-HT1A binding and release punished responding. Thus, the subpopulation of 5-HT1A receptors may mediate the behavioral effects of these compounds in animals and, in turn, the anxiolytic effects of buspirone and ipsapirone in humans. Although not primarily selective for 5-HT, lisuride may also mimic 8-OHDPAT by direct or indirect stimulation of 5-HT1A receptors.

Original languageEnglish (US)
Pages (from-to)29-36
Number of pages8
JournalEuropean Journal of Pharmacology
Volume138
Issue number1
DOIs
StatePublished - Jun 12 1987

Fingerprint

8-Hydroxy-2-(di-n-propylamino)tetralin
Anti-Anxiety Agents
Buspirone
Lisuride
Serotonin Receptor Agonists
Serotonin
Receptor, Serotonin, 5-HT1A
N,N-Dimethyltryptamine
Quipazine
Metergoline
2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
Methysergide
Ketanserin
Lysergic Acid Diethylamide
Serotonin Antagonists
Aptitude
Apomorphine
Prazosin
Dopamine Agonists
Clonidine

Keywords

  • 8-Hydroxy-2-(di-n-propylamino)tetralin (8-OHDPAT)
  • Anxiolytics
  • Drug discrimination
  • Serotonin
  • Serotonin receptors

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Discriminative stimulus properties of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OHDPAT) : implications for understanding the actions of novel anxiolytics. / Cunningham, Kathryn; Callahan, Patrick M.; Appel, James B.

In: European Journal of Pharmacology, Vol. 138, No. 1, 12.06.1987, p. 29-36.

Research output: Contribution to journalArticle

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