Prolonged treatment with 8-hydroxy-2-(di-n-propylamino)tetralin (8-OHDPAT) differently affects the serotonergic modulation of cortical acetylcholine release in male and female guinea pigs

Acetylcholine (ACh) release from the cerebral cortex was studied in freely moving guinea pigs, implanted with epidural cups. A single dose of either 8-hydroxy-2-(di-n-propylamino)tetralin (8-OHDPAT, 0.1 mg/kg s.c.) or 5-hydroxytryptamine (5-HT, 250 μg i.c.v.) increased cortical ACh release, both in male and in female guinea pigs. In female guinea pigs chronically treated with 8-OHDPAT (0.1 mg/kg daily s.c., for 14 days) the facilitatory effect of 8-OHDPAT and 5-HT was maintained. In chronically 8-OHDPAT-treated male guinea pigs, 8-OHDPAT no longer modified ACh release, while 5-HT inhibited it. The inhibition was prevented by the 5-HT₃ antagonist MDL 72222, 1 mg/kg s.c. These results indicate that differences exist between male and female guinea pigs in the adaptive responses to prolonged treatment with the selective 5-HT_1A agonist 8-OHDPAT.