Structure and function of the brain serotonin system

Jacobs, Barry L.; Azmitia, Efrain C.

doi:10.1152/physrev.1992.72.1.165

Cited by 2,306 publications

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“…Nevertheless, because ipsilateral mPFC stimulation in the present study produced similar increases in 5-HT output in the hippocampus and amygdala, and because contralateral stimulation also enhanced 5-HT efflux, the effects of mPFC stimulation on extracellular 5-HT levels seem to be mediated by a central structure, such as the raphe nuclei. In this context, the fact that the effects of contralateral stimulation were smaller than those of insilateral stimulation could be explained by the known lateralization of forebrain projections of serotonergic cells in the raphe nuclei (Jacobs and Azmitia 1992).…”

Section: Discussionmentioning

confidence: 99%

Electrical Stimulation of Rat Medial Prefrontal Cortex Enhances Forebrain Serotonin Output Implications for Electroconvulsive Therapy and Transcranial Magnetic Stimulation in Depression

Juckel

1999

Neuropsychopharmacology

103

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Decreased activity of the prefrontal cortex (PFC), as well as reduced serotonergic neurotransmission, is considered as a characteristic feature of major depression. The mechanism by which electroconvulsive therapy (ECT) and transcranial magnetic stimulation (TMS) achieve their antidepressant effects may involve changes in PFC activity. It is, however, still unclear whether these changes are accompanied by increased synaptic availability of serotonin (5-HT). In the present study, 5-HT efflux in the rat ventral hippocampus and amygdala was analyzed using in vivo microdialysis during low-current electrical stimulation of PFC and other cortical regions. Electrical stimulation of the medial PFC produced current-dependent increases in limbic 5-HT output in both urethane-anesthetized and behaving rats. No effects on 5-HT levels were seen after comparable stimulation of either the lateral parts of the PFCAn extensive body of clinical evidence suggests that prefrontal cortex (PFC) abnormalities are involved in the pathophysiology of major depression. Significantly decreased cerebral blood flow as well as reduced rates of glucose metabolism have been consistently found in the PFC of depressed patients (Soares and Mann 1997;Kennedy et al. 1997;George et al. 1993). This reduction seems to be localized predominantly in the left hemisphere (Baxter et al. 1989;Martinot et al. 1990). This is supported by structural neuroimaging studies demonstrating that poststroke depression is more likely to occur following a lesion in the left PFC rather than either in the right PFC or elsewhere in the left hemisphere (Morris et al. 1996;Robinson et al. 1984). Both neuropsychological and oculomotor functioning of prefrontal cortex is impaired in depression (Goodwin 1997;Sweeney et al. 1998). Furthermore, symptom improvement and remission of depressed patients have been associated with increases in cerebral blood flow and glucose metabolism in this region (Goodwin et al. 1993;Bench et al. 1995;Bonne and Krausz 1997;Buchsbaum et al. 1997 NO . 3 This close association between prefrontal cortical dysfunction and depression suggests that enhancement of PFC activity might be beneficial in the treatment of this disorder. Consistent with this idea, electroconvulsive therapy (ECT), as well as transcranial magnetic stimulation (TMS), seems to achieve its antidepressant effects by altering PFC activity. ECT leads to pronounced prefrontal EEG changes, which are directly related to the therapeutic outcome. Hence, the efficacy of ECT seems to be critically linked to prefrontal cortex involvement in ECT-induced seizure activity (Sackeim et al. 1996). This is further supported by studies that have reported changes in cerebral blood flow in prefrontal cortex of ECT responders (Nobler et al. 1994;Bonne et al. 1996;Petracca et al. 1995). In recent years, repetitive TMS of the left dorsolateral prefrontal cortex has emerged as a successful antidepressant treatment (Pascual-Leone et al. 1996;George et al. 1997). Although the exact mechanism underlying the ef...

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Section: Discussionmentioning

confidence: 99%

Electrical Stimulation of Rat Medial Prefrontal Cortex Enhances Forebrain Serotonin Output Implications for Electroconvulsive Therapy and Transcranial Magnetic Stimulation in Depression

Juckel

1999

Neuropsychopharmacology

103

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“…However, substantial evidence points to the heterogeneous nature of the DRN. For example, the proportion of 5-HT-containing cells in the DRN is estimated to range from one to two thirds (Steinbusch et al, 1980;Descarries et al, 1982;Jacobs and Azmitia, 1992;Baumgarten and Grozdanovic, 1997). The remaining non-serotonergic cells contain a variety of other neurotransmitters and neuromodulators including dopamine, norepinephrine, glutamate, *Corresponding author: Tel: +1-215-590-0656; fax: +1-215-590-0109.…”

Section: Introductionmentioning

confidence: 99%

Distinguishing characteristics of serotonin and non-serotonin-containing cells in the dorsal raphe nucleus: electrophysiological and immunohistochemical studies

et al. 2003

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The membrane properties and receptor-mediated responses of rat dorsal raphe nucleus neurons were measured using intracellular recording techniques in a slice preparation. After each experiment, the recorded neuron was filled with neurobiotin and immunohistochemically identified as 5-hydroxytryptamine (5-HT)-immunopositive or 5-HT-immunonegative. The cellular characteristics of all recorded neurons conformed to previously determined classic properties of serotonergic dorsal raphe nucleus neurons: slow, rhythmic activity in spontaneously active cells, broad action potential and large afterhyperpolarization potential. Two electrophysiological characteristics were identified that distinguished 5-HT from non-5-HT-containing cells in this study. In 5-HT-immunopositive cells, the initial phase of the afterhyperpolarization potential was gradual (tau=7.3±1.9) and in 5-HTimmunonegative cells it was abrupt (tau=1.8±0.6). In addition, 5-HT-immunopositive cells had a shorter membrane time constant (tau=21.4±4.4) than 5-HT-immunonegative cells (tau=33.5±4.2). Interestingly, almost all recorded neurons were hyperpolarized in response to stimulation of the inhibitory 5-HT 1A receptor. These results suggested that 5-HT 1A receptors are present on non-5-HT as well as 5-HT neurons. This was confirmed by immunohistochemistry showing that although the majority of 5-HT-immunopositive cells in the dorsal raphe nucleus were double-labeled for 5-HT 1A receptor-IR, a small but significant population of 5-HT-immunonegative cells expressed the 5-HT 1A receptor. These results underscore the heterogeneous nature of the dorsal raphe nucleus and highlight two membrane properties that may better distinguish 5-HT from non-5-HT cells than those typically reported in the literature. In addition, these results present electrophysiological and anatomical evidence for the presence of 5-HT 1A receptors on non-5-HT neurons in the dorsal raphe nucleus.Keywords 5-HT; 5-HT 1A receptor; intracellular; slice; rat The dorsal raphe nucleus (DRN) is generally considered a serotonergic nucleus because it is the largest source of 5-hydroxytryptamine (5-HT) terminals in the forebrain. However, substantial evidence points to the heterogeneous nature of the DRN. For example, the proportion of 5-HT-containing cells in the DRN is estimated to range from one to two thirds (Steinbusch et al., 1980;Descarries et al., 1982;Jacobs and Azmitia, 1992;Baumgarten and Grozdanovic, 1997). The remaining non-serotonergic cells contain a variety of other neurotransmitters and neuromodulators including dopamine, norepinephrine, glutamate, *Corresponding author: Tel: +1-215-590-0656; fax: +1-215-590-0109. kirbyl@email.chop.edu (L. G. Kirby). NIH Public Access Author ManuscriptNeuroscience. Author manuscript; available in PMC 2010 March 5. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptGABA, enkephalin, substance P, neuropeptide Y, thyrotropin-releasing hormone, vasoactive intestinal polypeptide, cholecystokinin, gastrin and neurotensin (for review...

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“…Serotonergic (5-HT) projections, arising from the midbrain raphe nuclei (Jacobs and Azmitia 1992;Vertes 1991) innervate limbic (amygdala and hippocampus) and cortical areas known to be involved in the cognition and processing of emotional events (Ambrogi Lorenzini et al 1998;Gallagher and Chiba 1996;Heilman and Gilmore 1998;Lavond et al 1993;Ledoux and Müller 1997;Pezzone et al 1992).…”

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confidence: 99%

Multiple 5-HT Receptors in Passive Avoidance Comparative Studies of p-Chloroamphetamine and 8-OH-DPAT

Misane

2000

Neuropsychopharmacology

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KEY WORDS : Passive avoidance; 5-HT receptors; 8-OH-DPAT; p-chloroamphetamine (PCA); m-chlorophenylpiperazine (mCPP); dopamineSerotonergic (5-HT) projections, arising from the midbrain raphe nuclei (Jacobs and Azmitia 1992; Vertes 1991) innervate limbic (amygdala and hippocampus) and cortical areas known to be involved in the cognition and processing of emotional events (Ambrogi Lorenzini et al. 1998;Gallagher and Chiba 1996;Heilman and Gilmore 1998;Lavond et al. 1993;Ledoux and Müller 1997;Pezzone et al. 1992).To investigate the role of the limbic and cortical 5-HT in behavior, different appproaches have been employed ranging from manipulations that result in multiple re- Received December 23, 1998; revised May 18, 1999; accepted July 13, 1999. N EUROPSYCHOPHARMACOLOGY 2000 -VOL . 22 , NO . 2 Multiple 5-HT Receptors in Passive Avoidance 169 ceptor stimulation to the selective activation of 5-HT receptor subtypes. The former approach is of particular importance, because 5-HT neurotransmission seems to operate largely via non-or extrasynaptic mode of communication, also known as volume transmission (Agnati et al. 1995;Bunin and Wightman 1998;Descarries et al. 1990;Descarries et al. 1975;Dewar et al. 1991;Jansson et al. 1998). Thus, released 5-HT can act at a distance at multiple 5-HT receptors far away from the synaptic cleft, whereas selective 5-HT agonists act on all receptors of a specific subtype.Earlier studies have shown that treatments that increase 5-HT activity in the brain, such as 5-HT-releasing compounds [p-chloroamphetamine (PCA), MDMA, and MMAI] (Marona- Lewicka et al. 1996;McNamara et al. 1995;Ögren 1985b;Romano and Harvey 1994;Santucci et al. 1996) as well as the selective 5-HT reuptake inhibitors (SSRIs) (Altman et al. 1984;Lalonde and Vikis-Freibergs 1985;Lucki and Nobler 1985;McElroy et al. 1982;Meneses and Hong 1995;Ögren 1985b) can both enhance and impair performance in aversive learning tasks. Pretraining administration of PCA has been found to produce a marked impairment of both one-and two-way active avoidance acquisition and retention in the rat (Ögren 1982).Although PCA also causes an acute release of dopamine (DA) (Crespi et al. 1997;Henderson et al. 1993;Johnson et al. 1990;Ögren 1985b;Sharp et al. 1986) as well noradrenaline (NA) (Ögren 1982; Ögren 1985a) in the rat brain, its behavioral effects are mediated primarily via serotonergic mechanisms (Adell et al. 1989;Geyer 1996;Hutson and Curzon 1989;Trulson and Jacobs 1976). In support of this, the one-way active avoidance deficit by PCA was completely blocked when the rats were pretreated with 5-HT reuptake inhibitors zimeldine and fluoxetine but not by the NA uptake inhibitor desipramine (Ögren 1982). Zimeldine also blocked the 5-HT release induced by PCA (Ögren et al. 1982). Several nonselective 5-HT 2 antagonists, which, by themselves, did not impair avoidance learning, also produced a dose-dependent blockade of the PCAinduced deficit (Ögren 1986b). This finding suggested that the impairment of active avoidance acquisit...

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Structure and function of the brain serotonin system

Cited by 2,306 publications

References 41 publications

Electrical Stimulation of Rat Medial Prefrontal Cortex Enhances Forebrain Serotonin Output Implications for Electroconvulsive Therapy and Transcranial Magnetic Stimulation in Depression

Electrical Stimulation of Rat Medial Prefrontal Cortex Enhances Forebrain Serotonin Output Implications for Electroconvulsive Therapy and Transcranial Magnetic Stimulation in Depression

Distinguishing characteristics of serotonin and non-serotonin-containing cells in the dorsal raphe nucleus: electrophysiological and immunohistochemical studies

Multiple 5-HT Receptors in Passive Avoidance Comparative Studies of p-Chloroamphetamine and 8-OH-DPAT

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