Serotonergic regulation of associative learning.

This paper presents a review of studies dealing with the effects of 5-HT agonists and antagonists on learning as measured by classical conditioning of the rabbit's nictitating membrane response or the conditioned avoidance response in the rat. These studies indicate that the 5-HT2A/2C receptors are importantly involved in learning. In these behavioral paradigms, enhancement of learning is only produced by drugs that are agonists at the 5-HT2A/2C receptors, and this enhancement is only blocked by drugs that are antagonists at these receptors. In addition, evidence is presented for the existence of two classes of 5-HT2A/2C antagonists consisting of negative antagonists that retard learning when given alone (ritanserin, MDL-11,939, pizotifen and cyproheptadine) and those that are neutral antagonists in that they have no effect on learning (ketanserin, mianserin, BOL and LY-53,857). However, both the neutral and negative antagonists are equally capable of blocking the enhancement of learning produced by 5-HT2A/2C agonists. It was concluded that 5-HT2A and/or 5-HT2C agonists may provide a new approach to the treatment of learning disorders in aging or Alzheimer's disease.