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3 5-HT projections throughout the human brain originating from the raphe nuclei in the midbrain

3 5-HT projections throughout the human brain originating from the raphe nuclei in the midbrain

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Effects of 2-bromoterguride, a dopamine D2 receptor partial agonist, in animal models of negative symptoms and cognitive dysfunctions associated with schizophrenia Inaugural-Dissertation zur Erlangung des akademischen Doktorgrades philosophiae doctor (Ph.D.) in 'Biomedical Science' an der Freien

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... is associated with structural and functional abnormalities in different parts of the brain (see Figure 2.1). The symptoms of schizophrenia are believed to derive from altered neurotransmission, i.e. compromised functional integration between cerebral subsystems (Dawson et al., 2014). ...
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... neurons, originating from the midbrain, distribute projections to different parts of the brain via four main pathways (Figure 2.2). The nigrostriatal dopamine pathway, from the substantia nigra to the dorsal striatum is indispensable for muscle movement and motor coordination (Williams et al., 2014). ...
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... is one of the most widely distributed neurochemical in the CNS and derives nearly entirely from the dorsal and median nucleus of the dorsal raphe, situated in the brain stem (Lucki, 1998;Siegel & Crockett, 2013). The number of 5-HT carrying neurons in the brain are relatively few, however, the extensive projections from the raphe innervate regions throughout the complete CNS (Breier, 1995; Figure 2.3). 5-HT neurons are autoactive neurons, which facilitate the central motor tone and fire continuously at a rate of 0.5 to 2.5 spikes/sec. ...
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... triggered neurotransmission is permitted via metabotropic G protein-coupled receptors and ionotropic ligand-gated ion-channels, each subdivided into three groups (see Figure 2.4). The structure and function of the metabotropic glutamate receptors (mGluR) are diverse and the receptors are found both pre-and postsynaptic, working either excitatory or inhibitory (Blackshaw et al., 2011). ...
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... receptors localized on neurons or glial cells are extensively dispersed throughout the brain and modulated by various endogenous ligands and ions (Lang et al., 2007). The cortical glutamate projections innervate throughout much of the cerebrum (see Figure 2.5). Glutamate pathways are descending from prefrontal to brainstem areas (dorsal-and medial raphe, VTA, substantia nigra); from the prefrontal cortex to striatum and nucleus accumbens; throughout the thalamocortical pathway (from thalamus to cortical pyramidal neurons); as well as the backward projections ascending from cortex to thalamus and the intra-cortical glutamate projections. ...
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... pathways are descending from prefrontal to brainstem areas (dorsal-and medial raphe, VTA, substantia nigra); from the prefrontal cortex to striatum and nucleus accumbens; throughout the thalamocortical pathway (from thalamus to cortical pyramidal neurons); as well as the backward projections ascending from cortex to thalamus and the intra-cortical glutamate projections. The GABAergic projections are widely distributed throughout the brain (see Figure 2.5), with pathways from the striatum descending to the substantia nigra and the brainstem; innervating the thalamus from the substantia nigra; originating in the hypothalamus descending to the occipital cortex and parietal cortex; projecting from the hippocampus to thalamus and striatum; from nucleus accumbens to thalamus and from the VTA to the prefrontal cortex, nucleus accumbens and other regions ( Hnasko et al., 2012;Barth et al., 2015). ...
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... < 0.001). 2-Bromoterguride (0.3 mg/kg) prevented the apomorphine-induced PPI deficits at 78, 82, and 86 dB (p < 0.003 each), an effect that was elicited by haloperidol (0.1 mg/kg) at 74 (p = 0.044), 78, 82, and 86 dB (p < 0.002 each) (Figure 4.2a). Further, 2-bromoterguride and clozapine attenuated PPI deficits induced by PCP. ...
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... hoc comparisons revealed that both doses of 2-bromoterguride and clozapine ameliorated the PPI impairment at 82 dB (0.1 mg/kg: p < 0.007; 0.3 mg/kg: p < 0.009; clozapine: p = 0.017). Additionally, 0.3 mg/kg 2-bromoterguride was also effective with a prepulse of 86 dB (p < 0.034) (Figure 4.2b). The ASR magnitude was affected by the factor treatment (F(4,132) = 4.5, p = 0.004). ...
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... illustrated in Chapter 4.4.1 (Figure 4.2a), apomorphine significantly reduced PPI compared to controls. In agreement with the observations of Davis et al. (1990), the largest reductions in PPI by apomorphine were detected for the weaker prepulse tones (4 and 8 dB above background). ...