Medial Hypothalamic 5-Hydroxytryptamine (5-HT)_1AReceptors Regulate Neuroendocrine Responses to Stress and Exploratory Locomotor Activity: Application of Recombinant Adenovirus Containing 5-HT_1ASequences

Abstract

Our previous studies found that serotonin transporter (SERT) knock-out mice showed increased sensitivity to minor stress and increased anxiety-like behavior but reduced locomotor activity. These mice also showed decreased density of 5-hydroxytryptamine (5-HT 1A ) receptors in the hypothalamus, amygdala, and dorsal raphe.

Impaired Stress-Coping and Fear Extinction and Abnormal Corticolimbic Morphology in Serotonin Transporter Knock-Out Mice

“…In an interesting parallel with these data, the present study found increased depression-like behavior in 5-HTT KO mice after repeated but not acute exposure to forced swim stress. 5-HTT KO mice also exhibited exaggerated behavioral, neuroendocrine, and catecholamine responses to certain mild stressors such as saline injection or predator exposure that are in themselves insufficiently potent to affect WT mice (Tjurmina et al, 2002;Li et al, 2004;Adamec et al, 2006;Li, 2006). Although parallels between phenotypic data in KO mice and higher species must always be made with due caution (Cryan and Holmes, 2005), together these findings are consistent with a growing literature indicating that loss of 5-HTT gene function compromises the capacity to adaptively cope with environmental stress.…”

Lasting Syndrome of Depression Produced by Reduction in Serotonin Uptake during Postnatal Development: Evidence from Sleep, Stress, and Behavior

“…By enhancing serotoninergic autoinhibition (Pineyro and Blier, 1999), it likely contributes to the deficit in serotoninergic transmission found in depression models (Overstreet, 2002;El Yacoubi et al, 2003). This contrasts with the desensitization of the 5-HT 1A autoreceptors in mutant mice with a deletion of the serotonin transporter gene (Fabre et al, 2000;Bouali et al, 2003;Li et al, 2004;Alexandre et al, 2006;present study). Thus, the adult 5-HT 1A autoreceptor sensitivity is partly determined by the state of serotoninergic function during early life, as also observed for other determinants of the serotoninergic transmission (Hansen and Mikkelsen, 1998;Maciag et al, 2006a).…”

The moderation by the serotonin transporter gene of environmental adversity in the aetiology of mental illness: review and methodological analysis

“…20 The 5-HTT knockout animals also show exaggerated neuroendocrine reactions to acute stress similar to the HPA axis over reactivity in depressed humans. 22,23 The effect of 5-HTT knockout on anxietyand depression-like behaviours may be mediated by the absence of functional serotonin clearance mechanism during a vulnerable developmental period, 24 but can still be selectively reversed by pharmacological 5HT1A receptor blockage later in life suggesting a life-long modulatory involvement of the serotonergic system. 19 The anxious-depressive phenotype in 5-HTT knockout mice is associated with increased dendritic branching in the 'fear circuit' including the amygdala and limbic cortex.…”