Effects of LSD, ritanserin, 8-OH-DPAT, and lisuride on classical conditioning in the rabbit

d-Lysergic acid diethylamide (LSD), an agonist at the 5-HT(2A/2C) and 5-HT1A receptors, has previously been demonstrated to enhance associative learning as measured by accelerated acquisition of the rabbit's classically conditioned nictitating membrane (NM) response. The present study examined further the role of these receptors in the action of LSD. LSD (30 nmol/kg, I.V.) significantly enhanced conditioned response (CR) acquisition to both tone and light conditioned stimuli (CSs), while the 5-HT1A receptor agonists 8-hydroxy-2-(dipropylamino)tetralin (8-OH-DPAT; 50 and 200 nmol/kg) and lisuride (0.3-30 nmol/kg) had no effect. Ritanserin (6.7-6700 nmol/kg, S.C.), a selective 5-HT(2A/2C) receptor antagonist, retarded acquisition of CRs to both tone and light CSs in a dose-dependent manner. Ritanserin (6.7-670 nmol/kg, S.C.) also dose dependently antagonized the enhancement of CR conditioning produced by LSD (30 nmol/kg, I.V.) to both tone and light CSs. We conclude that the enhancement of CR acquisition by LSD was due to an action at the 5-HT(2A/2C) receptor. These results suggest that the 5-HT(2A/2C) receptor plays an important role in learning.