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Ipsapirone, a high-affinity ligand for the 5-hydroxytryptamine1A (5-HT1A) receptor subtype, has been shown to be a full agonist at presynaptic serotonergic sites and a partial agonist at postsynaptic sites. Several recent studies have examined the effects of chronic treatment with ipsapirone or other structurally related pyrimidinylpiperazine compounds, including buspirone and gepirone, on 5-HT1A binding sites with mixed results. Since the neural mechanism responsible for the anxiolytic and antidepressant properties of these compounds is currently uncertain, further investigation of this issue appeared warranted. [3H]8-hydroxy-2-(di-n-propylamino)-tetralin ([3H]8-OH-DPAT), a ligand specific for the 5-HT1A site, has been used successfully to label these sites using both membrane binding assays and autoradiography. Experiments were performed to determine whether chronic treatment with ipsapirone would differentially affect binding to 5-HT1A receptors at different brain sites. Rats were treated twice daily with ipsapirone (10 mg/kg i.p.) for 1 day or for 1, 2, or 3 weeks. Quantitative analyses were done of autoradiograms of in vitro [3H]8-OH-DPAT binding to selected brain regions. Binding in vehicle-treated rats was highest in the hippocampus, septal nucleus, interpeduncular nucleus, entorhinal cortex, and dorsal raphe nucleus. Following 3 weeks of treatment with ipsapirone, a large decline in binding was measured in the dorsal raphe nucleus. This decline was not seen with ipsapirone treatments for shorter periods. With the 3-week treatment, there were less robust declines in [3H]8-OH-DPAT binding in the entorhinal cortex and interpeduncular nucleus. Binding in the other brain regions analyzed was unaltered.(ABSTRACT TRUNCATED AT 250 WORDS)