Mechanisms of Serotonergic Affect Control

  • G. A. Kennett
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 294)


Early pharmacological studies suggested that 5-hydroxytryptamine (5-HT) might be involved in the regulation of mood and in particular of anxiety. Thus, lesions of serotonergic pathways using the specific 5-HT neurotoxins 5,6- or 5,7-dihydroxytryptamine (5,7-DHT) were reported to result in anxiolytic actions in various conflict paradigms (Pelham et al., 1977; Tye et al., 1977), although not all studies have confirmed these findings (Commissaris et al., 1981). The dorsal raphe may be of particular importance in this response since the injection of 5,7-DHT into this nucleus causes anxiolytic actions in either the conflict (Thiebot et al., 1984) or social interaction tests (File et al., 1978). The 5-HT synthesis inhibitor parachlorophenylalanine (PCPA) was also reported to have anxiolytic actions in both conflict and social interaction anxiety models (Robichaud and Sledge, 1969; Geller and Blum, 1970; File and Hyde, 1978), an effect reported to be reversed in the conflict test by the 5-HT precursor 5-hydroxytryptophan (5-HTP) (Stein et al., 1973). However, significant anxiolytic effects of PCPA have not been universally reported (Blakely and Parker, 1973; Cook and Sepinwall, 1975; Pelham et al., 1975; Kilts et al., 1982). Studies using receptor antagonists to reduce 5-HT function have produced even less clear results, probably due to the complexity of 5-HT receptor pharmacology and the lack of truly selective drugs. Nevertheless, some receptor antagonists have been reported to have anxiolytic actions. Thus the non-specific 5-HT antagonists methysergide, cyproheptadine and cinanserin (Hoyer, 1988) were reported by some to have anxiolytic actions in conflict tests (Graeff and Schoenfield, 1970; Stein et al., 1973; Geller et al., 1974; Cook and Sepinwall, 1975; Becker, 1986) but not by others (Commissaris and Rech, 1982; Kilts et al., 1982; Becker, 1986; Deacon and Gardner, 1986). Another non-specific 5-HT antagonist metergoline (Hoyer, 1988), has also been reported ineffective in conflict (Deacon and Gardner, 1986) and the social interaction test (File, 1981).


Generalize Anxiety Disorder Panic Disorder Dorsal Raphe Dorsal Raphe Nucleus Conflict Behavior 
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Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • G. A. Kennett
    • 1
    • 2
  1. 1.Dept. of NeurochemistryInstitute of NeurologyLondonUK
  2. 2.Beecham Pharmaceuticals Research DivisionHarlowUK

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