Studies on the Role of Central 5-HT Neurons in Avoidance Learning: A Behavioral and Biochemical Analysis

Abstract

The ascending 5-hydroxytryptamine (5-HT, serotonin) containing neurons first described by Fuxe et al.¹, which originate in the midbrain raphe nuclei and have a widespread distribution in the forebrain^2,3 have been implicated in avoidance learning and memory processes ^4,5,6,7,8,9. Treatments known to modulate 5-HT neurotransmission have been found to alter the acquisition and performance of a wide range of aversively motivated behaviors^10,11. Despite intensive research, however, the specific role of serotonin in aversive learning and memory processes is little understood. In recent years it has become increasingly clear that different methods used to manipulate 5-HT neurotransmission can produce highly variable effects on avoidance behavior in the rat even when the animals are tested in similar behavioral situations^11,12,13. The available data suggest that the variations in avoidance behavior following 5-HT manipulation depend on both the tools employed to alter 5-HT neurotransmission and the behavioral situation used for testing the animals¹¹. The same manipulation of central 5-HT has been shown to cause different effects on avoidance learning when the testing situation is varied. For example, systemic injection of pchlorophenylalanine (PCPA), a tryptophan hydroxylase inhibitor, has been reported to facilitate one-way avoidance acquisition^6,7, but was recently shown not to significantly affect two-way active avoidance acquisition ¹². On the other hand, electrolytic lesions of the midbrain raphe nuclei, which produce a marked reduction in forebrain 5-HT concentrations, but in contrast to PCPA do not affect peripheral 5-HT stores, have consistently been shown to facilitate two-way and to impair one-way avoidance acquisition ^11,14. Thus, reduction of brain 5-HT concentrations can produce highly variable effects on avoidance learning.