Full and partial 5-HT1A receptor agonists disrupt learning and performancein rats

As a means of characterizing the role of 5-hydroxytryptamine (5-HT1A) recep tors in learning, a full 5-HT1A receptor agonist, 8-hydroxy-dipropylaminote tralin (8-OH-DPAT), was administered both alone and in combination with two partial agonists (buspirone and 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)bu tyl] piperazine hydrobromide (NAN-190)) and a 5-HT1A receptor antagonist (p -MPPI) to rats responding under a multiple schedule of repeated acquisition and performance of response sequences. in addition, the effects of another 5-HT1A receptor agonist, (LY228729), were also studied under this same pro cedure. When administered alone, both 8-OH-DPAT (0.1-3.2 mg/kg) and LY22872 9 (0.32-3.2 mg/kg) dose dependently decreased overall response rate and inc reased the percentage of errors in the acquisition and performance componen ts. At the doses of each drug tested, both buspirone (0.32 or 1 mg/kg) and NAN-190 (1 or 3.2 mg/kg) also decreased overall response rate and increased the percentage of errors. However, the effects of these drugs differed acr oss behavioral components and dependent measures. The effects of buspirone and NAN-190 on rate and accuracy were also different when they were adminis tered in combination with 8-OH-DPAT. In contrast, p-MPPI (3.2 or 10 mg/kg) had little or no effect when administered alone and antagonized the effects of 8-OH-DPAT; shifting the dose-effect curves for both response rate and t he percentage of errors in both components to the right. Taken together, th ese results indicate that complex behaviors in rats are sensitive to disrup tion by drugs with both full and partial 5-HT1A receptor agonist properties , and that the effects of partial 5-HT1A receptor agonists on learning may be different depending on their efficacy at pre- and postsynaptic 5-HT1A re ceptors.