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‐hydroxytryptamine1A (5‐HT1A) receptors. The present study investigated (1) the discriminability of ipsapirone using a two‐lever, water‐reinforced task and (2) the importance of 5‐HT1A 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‐HT1A 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‐HT1A agonist, blockade of the ipsapirone cue by a 5‐HT1A antagonist remains to be established.

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

Keywords

  • 5‐HT receptors
  • catecholamines
  • drug discrimination
  • ipsapirone

ASJC Scopus subject areas

  • Drug Discovery

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