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

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.