Animal Models of Integrated Serotoninergic Functions: Their Predictive Value for the Clinical Applicability of Drugs Interfering with Serotoninergic Transmission

Studies of serotonin in the brain began in the early 1950s, when Twarog and Page (1953) used a sensitive bioassay to detect the compound’s presence in cerebral tissue. Shortly afterwards, a possible central role for serotonin in mental illness was evoked by Wooley and Shaw (1954), based principally on the psychotomimetic activity of lysergic acid diethylamide (LSD), which had been found to antagonize the effects of serotonin on smooth muscle. Since this time, there has been an intense research effort towards an understanding of this neurotransmitter, and it is now clear that serotoninergic systems are implicated to various extents in the expression of a wide range of CNS functions, including neuronal development (Lauder 1983), thermoregulation (Feldberg and Myers 1964), pain (Tenen 1967), motor regulation (Jacobs 1991), sleep (Jouvet 1967), appetite (Fernstrom and Wurtman 1971), sexual behaviour (Gorzalka et al. 1990), aggression (Sheard 1969; Soubrie 1986), anxiety (Chopin and Briley 1987) and mood (Golden and Gilmore 1990).