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Theories of the Etiology of Anxiety
Published in Siegfried Kasper, Johan A. den Boer, J. M. Ad Sitsen, Handbook of Depression and Anxiety, 2003
Trevor R. Norman, Graham D. Burrows, James S. Olver
Much of the evidence for a role of serotonin in anxiety states relies on data from animal studies. It is well recognized that the main cell bodies of serotonin-containing neurons arise in the brainstem and innervate virtually all cortical areas. Both the dorsal and median raphe nuclei contain cell bodies that give rise to ascending serotonergic pathways. Within this broad anatomical framework there are subtle functional connections of neurons [94]. Coupled with a plethora of serotonin receptor subtypes, it is clear that the serotonergic system provides multiple anxiogenic/anxiolytic targets.
A potential paradigm shift in opioid crisis management: The role of pharmacogenomics
Published in The World Journal of Biological Psychiatry, 2022
David Eapen-John, Ayeshah G. Mohiuddin, James L. Kennedy
Serotonin released from the median raphe nucleus acts on dopaminergic centres in the limbic system. Serotonin is known to have numerous effects in the brain, but it is hypothesised that serotonin and dopamine serve reciprocal functions, with dopamine inducing appetitive or seeking behaviours, and serotonin countering these effects by inhibiting dopaminergic activity (Esposito et al. 2008). A major point of serotonin regulation is at the serotonin transporter (SERT), encoded by the gene SLC6A4. This transporter protein serves to remove serotonin from the synaptic cleft and recycle it into storage in the presynaptic neuron (Yuferov et al. 2021). Variation in dopamine receptor genes and serotonin transporter genes may alter an individual’s tendency for addictive behaviours, such as opioid abuse and may provide useful information regarding the individualised risk of opioid prescription for pain management.
Decreased tryptophan hydroxylase 2 mRNA and protein expression, decreased brain serotonin concentrations, and anxiety-like behavioral changes in a rat model of simulated transport stress
Published in Stress, 2019
Lili Wang, Deping Han, Peng Yin, Kedao Teng, Jianqin Xu, Yunfei Ma
The serotonergic system is widely distributed in the central nervous system (CNS) and plays a vital role in many physiological functions, such as cardiovascular regulation, respiration, and thermoregulation, and psychological functions, including circadian rhythms, appetite, aggression, mood, cognition, learning, and memory (Miura et al., 2008; Sodhi & Sanders-Bush, 2004). In mammals, 5-hydroxytryptamine-producing neurons in the dorsal raphe (DR) and median raphe nuclei principally innervate the forebrain regions and are involved in stress responses. Moreover, 5-hydroxytryptamine neurons receive input from other brain structures, including the hypothalamus, prefrontal cortex, and the bed nucleus of the stria terminalis, to provide a feedback control for 5-hydroxytryptamine release (Booij, Tremblay, Szyf, & Benkelfat, 2015). The DR is located in the rostral pontine and caudal midbrain tegmentum and can be divided into six subregions based on the cytoarchitecture and distribution of the serotonergic neurons: the rostral (DRr), dorsal (DRD), ventral (DRv), lateral (DRL), caudal (DRc), and interfascicular (DRI) parts. The DRD can be further divided into two subregions, namely the DRD core region (DRDc) and the DRD shell region (DRDsh) (Baker, Halliday, & Tork, 1990; Hioki et al., 2010; Lowry et al., 2008).
Activation and blockade of dorsal hippocampal Serotonin6 receptors regulate anxiety-like behaviors in a unilateral 6-hydroxydopamine rat model of Parkinson’s disease
Published in Neurological Research, 2019
Kun Cheng Liu, Yuan Guo, Jin Zhang, Li Chen, Yi Wei Liu, Shu Xuan Lv, Wen Xie, Hui Sheng Wang, Yu Ming Zhang, Li Zhang
The 5-HT neurotransmitter system is important in the modulation of anxiety [8], and it is well known that nigrostriatal pathway degeneration results in central 5-HT neurotransmitter system dysfunction [40,41]. The 5-HT fibers from the median raphe nucleus project densely to the dHip [10]. The hippocampus plays a critical role in the pathophysiology of anxiety [9,42] and controls the drive of the amygdala to the prefrontal cortex [43]. The dHip is believed to take part in the regulation of anxiety-related behaviors [8,9,44]. 5-HT6 receptors have moderate to high densities in the dHip [13,14,20]. A few studies have reported the involvement of 5-HT6 receptors in anxiety, however, their results are inconsistent [17,18]. In addition, 5-HT6 receptor agonists and antagonists have been reported to produce similar anxiolytic-like effects in rodents [8,9,19,45]. Further, several studies have found that intra-hippocampus administration of the 5-HT6 receptor agonist EMD 386088 and antagonist SB258585 in rats produce anxiolytic-like effects [8,9]. These studies suggest that 5-HT6 receptors play an important role in regulating anxiety in rats. Although 5-HT6 receptors in the hippocampus are known to have a role in regulating anxiety, the effects of dHip 5-HT6 receptors on anxiety-like behaviors in parkinsonian rats are unknown. In the present study, intra-dHip injection of the 5-HT6 receptor agonist WAY208466 or antagonist SB258585 induced anxiolytic actions in sham-operated rats, a finding that is consistent with other recent reports [8,9]. However, we found that intra-dHip injection of WAY208466 induced anxiolytic effects in the 6-OHDA lesioned rats, and SB258585 induced anxiety-like effects.