Vol. 288, Issue 1, 335-347, January 1999

Full and Partial 5-HT_1A Receptor Agonists Disrupt Learning and Performance in Rats

P. J. Winsauer, F. H. Rodriguez, A. E. Cha and J. M. Moerschbaecher

Department of Pharmacology and Experimental Therapeutics, Louisiana State University Medical Center, New Orleans, Louisiana

As a means of characterizing the role of 5-hydroxytryptamine (5-HT_1A) receptors in learning, a full 5-HT_1A receptor agonist, 8-hydroxy-dipropylaminotetralin (8-OH-DPAT), was administered both alone and in combination with two partial agonists (buspirone and 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl] piperazine hydrobromide (NAN-190)) and a 5-HT_1A 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-HT_1A receptor agonist, (LY228729), were also studied under this same procedure. When administered alone, both 8-OH-DPAT (0.1-3.2 mg/kg) and LY228729 (0.32-3.2 mg/kg) dose dependently decreased overall response rate and increased the percentage of errors in the acquisition and performance components. 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 across behavioral components and dependent measures. The effects of buspirone and NAN-190 on rate and accuracy were also different when they were administered 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 the percentage of errors in both components to the right. Taken together, these results indicate that complex behaviors in rats are sensitive to disruption by drugs with both full and partial 5-HT_1A receptor agonist properties, and that the effects of partial 5-HT_1A receptor agonists on learning may be different depending on their efficacy at pre- and postsynaptic 5-HT_1A receptors.