Neuropharmacological assessment of the discriminative stimulus properties of the novel anxiolytic ipsapirone

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Abstract

The novel anxiolytic ipsapirone appears to interact selectively with 5-hydroxytryptamine(1A) (5-HT(1A)) receptors. The present study investigated 1) the discriminability of ipsapirone using a two-lever, water-reinforced task and 2) the importance of 5-HT(1A) and catecholamine systems in the ipsapirone cue. To this end, rats were trained to discriminate ipsapirone (7.5 mg/kg; N = 14) from saline. Dose-response tests indicated that the ipsapirone cue was dose dependent. Buspirone and 8-OH DPAT substituted while the dopamine (DA) D1 agonist SKF 38393, the DA D2 agonist quinpirole, and the α2-adrenoceptor agonist clonidine engendered saline responding. Furthermore, the D1 antagonist SCH 23390, the D2 antagonist sulpiride, and the putative 5-HT(1A) antagonist spiroxatrine did not block or mimic the ipsapirone cue. This research suggests that catecholamine systems do not play a prominent role in mediating the stimulus properties of ipsapirone. Moreover, while the substitution profile for ipsapirone suggests that this novel anxiolytic may be a selective 5-HT(1A) agonist, blockade of the ipsapirone cue by a 5-HT(1A) antagonist remains to be established.

Original languageEnglish (US)
Pages (from-to)345-353
Number of pages9
JournalDrug Development Research
Volume16
Issue number2-4
StatePublished - 1989

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Anti-Anxiety Agents
Cues
Serotonin
Serotonin Antagonists
spiroxatrine
Dopamine Agonists
Catecholamines
Dopamine
2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
Quinpirole
Buspirone
ipsapirone
8-Hydroxy-2-(di-n-propylamino)tetralin
Serotonin Receptor Agonists
Sulpiride
Receptor, Serotonin, 5-HT1A
Clonidine
Adrenergic Receptors
Rats
Substitution reactions

ASJC Scopus subject areas

  • Organic Chemistry
  • Drug Discovery
  • Pharmacology

Cite this

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abstract = "The novel anxiolytic ipsapirone appears to interact selectively with 5-hydroxytryptamine(1A) (5-HT(1A)) receptors. The present study investigated 1) the discriminability of ipsapirone using a two-lever, water-reinforced task and 2) the importance of 5-HT(1A) and catecholamine systems in the ipsapirone cue. To this end, rats were trained to discriminate ipsapirone (7.5 mg/kg; N = 14) from saline. Dose-response tests indicated that the ipsapirone cue was dose dependent. Buspirone and 8-OH DPAT substituted while the dopamine (DA) D1 agonist SKF 38393, the DA D2 agonist quinpirole, and the α2-adrenoceptor agonist clonidine engendered saline responding. Furthermore, the D1 antagonist SCH 23390, the D2 antagonist sulpiride, and the putative 5-HT(1A) antagonist spiroxatrine did not block or mimic the ipsapirone cue. This research suggests that catecholamine systems do not play a prominent role in mediating the stimulus properties of ipsapirone. Moreover, while the substitution profile for ipsapirone suggests that this novel anxiolytic may be a selective 5-HT(1A) agonist, blockade of the ipsapirone cue by a 5-HT(1A) antagonist remains to be established.",
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AB - The novel anxiolytic ipsapirone appears to interact selectively with 5-hydroxytryptamine(1A) (5-HT(1A)) receptors. The present study investigated 1) the discriminability of ipsapirone using a two-lever, water-reinforced task and 2) the importance of 5-HT(1A) and catecholamine systems in the ipsapirone cue. To this end, rats were trained to discriminate ipsapirone (7.5 mg/kg; N = 14) from saline. Dose-response tests indicated that the ipsapirone cue was dose dependent. Buspirone and 8-OH DPAT substituted while the dopamine (DA) D1 agonist SKF 38393, the DA D2 agonist quinpirole, and the α2-adrenoceptor agonist clonidine engendered saline responding. Furthermore, the D1 antagonist SCH 23390, the D2 antagonist sulpiride, and the putative 5-HT(1A) antagonist spiroxatrine did not block or mimic the ipsapirone cue. This research suggests that catecholamine systems do not play a prominent role in mediating the stimulus properties of ipsapirone. Moreover, while the substitution profile for ipsapirone suggests that this novel anxiolytic may be a selective 5-HT(1A) agonist, blockade of the ipsapirone cue by a 5-HT(1A) antagonist remains to be established.

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