The role of hippocampal 5-hydroxytryptamine 1A (5-HT1A) receptors in the anticonflict activity of beta-adrenoceptor antagonists.

The nonselective beta-adrenoceptor antagonists pindolol and cyanopindolol, which bind to 5-HT1A and 5-HT1A receptors showed an anticonflict effect by increasing the number of punished licks in the Vogel conflict test in rats, when administered directly into the CA, region of the dorsal hippocampus (i.hp.). The maximum effect was observed after intrusion of 1 microgram of pindolol and 3 microgram of cyanopindolol. However, the selective beta 1-and beta2-adrenoceptor antagonists betaxolol and ICI 118,551, respectively, which have a negligible affinity for 5-HT receptors, did not affect the punished responding, when administered i.hp. in doses up to 10 micrograms. The anticonflict effect of pindolol (1 microgram) was significantly reduced by (S)-WAY 100135, a selective 5-HT1A-receptor antagonist, administered i.hp (0.1 microgram) or s.c. (10 mg/kg). Furthermore, (S)-WAY 100135 injected i.hp (0.3 micrograms) significantly antagonized the anticonflict effect of pindolol injected i.p. (8 mg/kg). (S)-WAY 100135 given alone i.hp. (0.03-3 micrograms) or s.c. (5-10 mg/kg) did not affect the punished responding in rats. These results indicate that the anticonflict effect of the beta-blockers which were tested, or at least pindolol, depends on their agonist action on postsynaptic 5-HT1A receptors located in the hippocampus.