In this brief reflection I outline how Fred Graeff and I came to integrate our ideas and findings concerning the behavioural functions of serotonin (5-HT) over 20 years ago in ‘5-HT and mechanisms of defence’, reproduced in this volume (pp. 000-000). The principal insight was that different 5-HT pathways mediate distinct adaptive responses to aversive events of different types. It emerged from a number of strands in neuropsychopharmacology: the functional implications of the still-fresh images of monoamine neuroanatomy of the 1970s; the ethological differentiation of behavioural responses to proximal and distal threats; and the seemingly contradictory effects of 5-HT drugs in unconditioned, Pavlovian and instrumental paradigms of reward and aversion. The article has been cited over 600 times and continues to be cited. The evidence was mainly from the animal literature but included some experimental psychopharmacological tests in humans. Some more recent and notable human corroborations are highlighted in this perspective.
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