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Claudia Maria Padovan - One of the best experts on this subject based on the ideXlab platform.

  • attenuation of stress induced behavioral changes by activation of serotonin type 7 receptors in the Median Raphe Nucleus of rats
    Journal of Psychopharmacology, 2020
    Co-Authors: Willian Lazarinilopes, Fabiana Corsizuelli, Claudia Maria Padovan
    Abstract:

    Background Exposure to stressful aversive situations induces physiological and behavioral changes. Serotonin has been suggested to mediate such changes, as well as adaptation to stressful events. Serotoninergic projections arising from the Median Raphe Nucleus to the dorsal hippocampus have been suggested to promote adaptation to chronic aversive stimuli. Such pathway may involve serotonin type 1a receptor-mediated neurotransmission. However, the serotonin 7 receptor can also be found in the Median Raphe Nucleus and may be involved in mechanisms underlying response to stress. Aims In this work we sought to investigate if activation of serotonin type 7 receptors would attenuate stress-induced deficits in different animal models of depression. Methods Male Wistar rats with a guide-cannula aimed to the Median Raphe Nucleus were submitted to restraint or forced swim stress and were tested in an elevated plus maze or forced swim test, respectively, 24 h later. SB 258741 (serotonin type 7 receptor antagonist) and/or LP 44 (serotonin type 7 receptor agonist) were administered intra-Median Raphe Nucleus immediately before or after exposure to stress or before test. Control groups received intra-Median Raphe Nucleus treatment 24 h or immediately before test in the elevated plus maze or forced swim test. Results LP 44 attenuated restraint-induced exploratory deficits independently of the moment it was administered. Similar results were observed in the forced swim test, with the exception on post-stress condition. These effects on adaptation to stress induced by serotonin type 7 receptor activation were prevented by previous treatment with SB 258741. Conclusions Our data support the idea that activation of Median Raphe Nucleus serotonin 7 receptor is important to the development of adaptation to stress.

  • Attenuation of stress-induced behavioral changes by activation of serotonin type 7 receptors in the Median Raphe Nucleus of rats.
    Journal of psychopharmacology (Oxford England), 2020
    Co-Authors: Willian Lazarini-lopes, Fabiana Corsi-zuelli, Claudia Maria Padovan
    Abstract:

    Exposure to stressful aversive situations induces physiological and behavioral changes. Serotonin has been suggested to mediate such changes, as well as adaptation to stressful events. Serotoninergic projections arising from the Median Raphe Nucleus to the dorsal hippocampus have been suggested to promote adaptation to chronic aversive stimuli. Such pathway may involve serotonin type 1a receptor-mediated neurotransmission. However, the serotonin 7 receptor can also be found in the Median Raphe Nucleus and may be involved in mechanisms underlying response to stress. In this work we sought to investigate if activation of serotonin type 7 receptors would attenuate stress-induced deficits in different animal models of depression. Male Wistar rats with a guide-cannula aimed to the Median Raphe Nucleus were submitted to restraint or forced swim stress and were tested in an elevated plus maze or forced swim test, respectively, 24 h later. SB 258741 (serotonin type 7 receptor antagonist) and/or LP 44 (serotonin type 7 receptor agonist) were administered intra-Median Raphe Nucleus immediately before or after exposure to stress or before test. Control groups received intra-Median Raphe Nucleus treatment 24 h or immediately before test in the elevated plus maze or forced swim test. LP 44 attenuated restraint-induced exploratory deficits independently of the moment it was administered. Similar results were observed in the forced swim test, with the exception on post-stress condition. These effects on adaptation to stress induced by serotonin type 7 receptor activation were prevented by previous treatment with SB 258741. Our data support the idea that activation of Median Raphe Nucleus serotonin 7 receptor is important to the development of adaptation to stress.

  • role of serotonin 1a receptors in the Median Raphe Nucleus on the behavioral consequences of forced swim stress
    Journal of Psychopharmacology, 2013
    Co-Authors: P V G Almeida, Claudia Maria Padovan, M C Trovo, A M Tokumoto, A C Pereira
    Abstract:

    Despite the intense research on the neurobiology of stress, the role of serotonin (5-HT)1A receptors still remains to be elucidated. In the hippocampus, post-synaptic 5-HT1A receptors activation induces anxiolytic effects in animals previously exposed to stressful situations. However, little is known about somatodendritic 5-HT1A receptors in the Median Raphe Nucleus (MRN). Therefore, the aim of this study was to investigate the role of 5-HT1A receptors located in the MRN in rats exposed to forced swim stress. After recovering from surgery, rats were forced to swim for 15 min in a cylinder. Intra-MRN injections of saline, 8-OH-DPAT (3 nmol/0.2 µL) and/or WAY-100635 (0.3 nmol/0.2 µL) were performed immediately before or after pre-exposure or 24 h later (immediately before test). Non-stressed rats received the same treatment 24 h or 10 min before test. Our data showed that 8-OH-DPAT increased latency to display immobility while decreasing time spent immobile in almost all experimental conditions. These effec...

Fangchia Chang - One of the best experts on this subject based on the ideXlab platform.

  • disruption of footshock induced theta rhythms by stimulating Median Raphe Nucleus reduces anxiety in rats
    Behavioural Brain Research, 2013
    Co-Authors: Yitse Hsiao, Peilu Yi, Chiunghsiang Cheng, Fangchia Chang
    Abstract:

    Abstract Theta rhythms generated in the hippocampus are controlled by the pacemaker in the medial septum-diagonal band of Broca (MS-DBB). The Median Raphe Nucleus (MRN) transmits serotonergic signals to the MS-DBB, which suppresses the septo-hippocampus-produced theta waves, whereas GABAergic interneurons in the MRN facilitate the generation of theta oscillations. Animal studies have indicated that fear increases theta oscillations. Moreover, anxiolytics reduce reticular formation-elicited theta rhythms and theta blockade decreases anxiety. In this study, we hypothesized that the MRN mediates anxiety reduction caused by the theta blockade. Our results demonstrated that inescapable-footshock stimulation significantly increased the power of low-frequency theta oscillations (4–7 Hz) in rats. Both the electrical stimulation of MRN and administration of bicuculline into the MRN successfully desynchronized footshock-induced theta oscillations. Compared to the naive rats, inescapable-footshock stimulation diminished the entry percentage and time spent in the open arms of the elevated plus maze (EPM), behavioral indicators of anxiety. Rats treated with either MRN stimulation or bicuculline administration to desynchronize theta oscillations reduced anxiety caused by the inescapable-footshock stimulation. Our results demonstrated that the electrical stimulation of MRN or blockade of the GABAergic pathways in the MRN interferes with theta oscillations and reduces anxiety, implicating the role of MRN.

  • activation of gabaergic pathway by hypocretin in the Median Raphe Nucleus mrn mediates stress induced theta rhythm in rats
    Behavioural Brain Research, 2012
    Co-Authors: Yitse Hsiao, Peilu Yi, Fangchia Chang
    Abstract:

    Abstract The frequency of electroencephalograms (EEGs) is predominant in theta rhythm during stress (e.g., footshock) in rats. Median Raphe Nucleus (MRN) desynchronizes hippocampal theta waves via activation of GABAergic neurons in the medial septum-diagonal band of Broca (MS-DBB), a theta rhythm pacemaker. Increased hypocretin mediates stress responses in addition to the maintenance of wakefulness. Hypocretin receptors are abundant in the MRN, suggesting a possible role of hypocretin in modulating stress-induced theta rhythm. Our results indicated that the intensity of theta waves was enhanced by footshock and that a hypocretin receptor antagonist (TCS1102) suppressed the footshock-induced theta waves. Administration of hypocretin-1 (1 and 10 μg) and hypocretin-2 (10 μg) directly into the MRN simulated the effect of footshock and significantly increased theta waves. Co-administration of GABA A receptor antagonist, bicuculline, into the MRN blocked the increase of theta waves induced by hypocretins or footshock. These results suggested that stress enhances the release of hypocretins, activates GABAergic neurons in the MRN, blocks the ability of MRN to desynchronize theta waves, and subsequently increases the intensity of theta rhythm.

Bernat Kocsis - One of the best experts on this subject based on the ideXlab platform.

  • gabaergic control of the ascending input from the Median Raphe Nucleus to the limbic system
    Journal of Neurophysiology, 2005
    Co-Authors: Shaomin Li, Viktor Sebestyen Varga, Bernat Kocsis
    Abstract:

    The Median Raphe Nucleus (MRN) is the primary source of serotonergic afferents to the limbic system that are generally considered to suppress hippocampal theta oscillations. GABA receptors are expr...

  • discharge properties of neurons of the Median Raphe Nucleus during hippocampal theta rhythm in the rat
    Experimental Brain Research, 2002
    Co-Authors: Gonzalo Viana Di Prisco, Robert P. Vertes, Zimbul Albo, Bernat Kocsis
    Abstract:

    The serotonin (5-HT)-containing Median Raphe Nucleus has been shown to be critically involved in the control of desynchronized (non theta) states of the hippocampal electroencephalogram (EEG). We examined the activity of 181 cells of the Median Raphe Nucleus in the urethane-anesthetized rat and found that approximately 80% (145/181) of them showed changes in activity associated with changes in the hippocampal EEG. These cells were subdivided into theta-on (68%) and theta-off (32%) based on increased or decreased rates of activity with theta, respectively. They were further classified as slow-firing (~1 Hz), moderate-firing (5–11 Hz), or fast-firing (>12 Hz) theta-on or theta-off cells. The slow-firing cells as well as a subset of moderate-firing theta-off cells displayed characteristics of “classic” serotonin-containing Raphe neurons. All fast-firing neurons were theta-on cells and showed either tonic or phasic (rhythmical) increases in activity with theta. We propose that: (1) the slow-firing cells (on and off) as well as a subset of moderate-firing theta-off cells are serotonergic neurons; (2) the phasic and tonic fast-firing theta-on cells are GABAergic cells; and (3) these populations of cells mutually interact in the modulation of the hippocampal EEG. An activation of local serotonergic and GABAergic theta-on cells would inhibit 5-HT slow- or moderate-firing theta-off projection cells to release or generate theta, whereas the suppression of serotonergic- or GABAergic theta-on cells would disinhibit 5-HT theta-off cells, resulting in a blockade of theta or a desynchronization of the hippocampal EEG. A role for the Median Raphe Nucleus in memory-associated functions of the hippocampus is discussed.

  • gabab receptors in the Median Raphe Nucleus distribution and role in the serotonergic control of hippocampal activity
    Neuroscience, 2002
    Co-Authors: Viktor Sebestyen Varga, T F Freund, Bernat Kocsis
    Abstract:

    Abstract Previous studies have shown that serotonergic neurons of the Median Raphe Nucleus have a suppressive effect on theta synchronization in the hippocampus. Median Raphe lesion, suppression of 5-HT neuronal activity by administration of GABA A receptor antagonist or by glutamate blockade or depletion produced long-lasting non-interrupted hippocampal theta in freely behaving rats independent of behavior and in rats anesthetized with urethane. Serotonergic neurons show a characteristic sleep–wake pattern of activity and there is evidence that GABAergic mechanisms play an important role in their regulation. In this study we analyzed the distribution and subcellular localization of GABA B receptors in the midbrain Raphe complex using combined 5-HT/GABA B receptor immunohistochemistry at the light and electron microscopic levels and studied the effects of their pharmacological manipulation on hippocampal electroencephalographic activity in urethane-anesthetized rats. We found that sustained infusion of the GABA B receptor agonist baclofen into the Median Raphe Nucleus, using the microdialysis technique, elicited lasting theta activity in the hippocampus. The effect was antagonized by selective GABA B receptor antagonists. The predominant localization of GABA B receptors in the Median, as well as in dorsal Raphe was found on serotonergic neurons which strongly indicates that the increase in theta occurrence after baclofen injection resulted from suppression of the serotonergic output originating from the Median Raphe. On the electron microscopic level, we found GABA B receptors located extrasynaptically indicating that these receptors are preferentially activated by strong inputs, i.e. when GABA released from the synaptic terminals is sufficient to spill over from the synaptic cleft. Such conditions might be satisfied during rapid eye movement sleep when GABAergic neurons in the Raphe are firing at their highest rate and in rhythmic synchronized bursts. Our data indicate that midbrain Raphe GABA B mechanisms play an important role in behavioral state control and in hippocampal activity, in particular.

  • reduction of the extracellular level of glutamate in the Median Raphe Nucleus associated with hippocampal theta activity in the anaesthetized rat
    Neuroscience, 1998
    Co-Authors: Viktor Sebestyen Varga, A Kekesi, G Juhasz, Bernat Kocsis
    Abstract:

    Abstract The relationship between hippocampal activity and the extracellular level of excitatory amino acids in the Median Raphe Nucleus has been studied in urethane anaesthetized rats, using the in vivo microdialysis technique. Dialysates were collected from the Median Raphe Nucleus during two to eight sampling periods of equal length (20 min) and hippocampal electroencephalogram was continuously monitored. For each observation period, the average glutamate level in the Median Raphe Nucleus was determined and the percentage of theta and non-theta segments in the hippocampal recordings was calculated. Theta synchronization, in these experiments, either developed spontaneously or it was elicited by injection of anticholinesterase (Physostigmine or Sintostigmine, i.p.) or by a series of short tail pinches. The relationship between hippocampal activity and glutamate release in the Median Raphe Nucleus was characterized by comparison of the direction of changes in these two parameters in consecutive sampling periods. We found that as long as theta/non-theta ratio changed spontaneously or under the effect of anticholinesterase ( n =7), the extracellular level of glutamate in the Median Raphe Nucleus was elevated during periods dominated by desynchronized hippocampal activity as compared with those mostly containing long and/or frequently occurring theta segments. Such relationship was not observed in the adjacent reticular formation ( n =4) and in the Median Raphe Nucleus during sensory stimulation ( n =2). The present data complete those found earlier indicating that the desynchronizing serotonergic influence originating from the brainstem is maintained by a tonic excitatory input to the Median Raphe Nucleus. Since the majority of glutamatergic afferents to the Median Raphe Nucleus originates from the lateral habenula and the interpeduncular Nucleus, known to connect limbic forebrain to the brainstem, theta associated changes in Median Raphe Nucleus glutamate levels might reflect descending forebrain influences, suggesting therefore a feedback regulation of the hippocampal activity involving brainstem structures.

  • medial septal unit firing characteristics following injections of 8 oh dpat into the Median Raphe Nucleus
    Brain Research, 1996
    Co-Authors: Gene G. Kinney, Bernat Kocsis, Robert P. Vertes
    Abstract:

    Abstract Extracellular single-unit recording techniques were used to examine the firing characteristics of neurons in the medial septum/diagonal band of Broca complex (MS/1313) following injections of the 5-HT1A agonist, 8-OH-DPAT, into the Median Raphe Nucleus (MRN) of urethane-anesthetized rats. It had previously been shown that MRN injections of 8-OH-DPAT produce hippocampal theta rhythm. Injections of 8-OH-DPAT into the MRN produced a change in firing characteristics of MS/1313 neurons from an irregular discharge to a pattern of rhythmical bursting in synchrony with hippocampal theta rhythm. Cross-correlational and coherence analyses demonstrated that the rhythmical firing pattern of MS/1313 neurons strongly correlated with rhythmical fluctuations in the hippocampal EEG during periods of hippocampal theta produced by 8-OH-DPAT injections, but not during baseline conditions (i.e. hippocampal desynchronization). The results suggest that MRN control of the hippocampal EEG is modulated by the MS/DB. Serotonergic projections from the MRN to the MS/DB may normally act to inhibit the rhythmical bursting of MS/1313 neurons, thereby producing hippocampal desynchronization. Suppression of MRN 5-HT neurons by MRN injections of 8-OH-DPAT would disinhibit MS/1313 neurons, allowing them to burst rhythmically and thereby produce hippocampal theta rhythm.

Paul J Fletcher - One of the best experts on this subject based on the ideXlab platform.

  • intra Median Raphe Nucleus mrn infusions of muscimol a gaba a receptor agonist reinstate alcohol seeking in rats role of impulsivity and reward
    Psychopharmacology, 2007
    Co-Authors: Douglas Funk, Zhaoxia Li, Anh Le Dzung, Stephen E Harding, W Juzytsch, Paul J Fletcher
    Abstract:

    Rationale and objectives We previously found that the inhibition of Median Raphe Nucleus (MRN) 5-HT transmission by local injections of a 5-HT1A agonist 8-OH-DPAT or corticotrophin-releasing factor (CRF) mimic the effect of foot shock stress to reinstate alcohol seeking. In this study, we further explored the role of the MRN by examining the effect of inhibition of MRN neurons, by injecting the GABA-A receptor agonist muscimol, on the reinstatement of alcohol seeking.

  • the role of corticotropin releasing factor in the Median Raphe Nucleus in relapse to alcohol
    The Journal of Neuroscience, 2002
    Co-Authors: A D Le, Stephen E Harding, W Juzytsch, Paul J Fletcher, Yavin Shaham
    Abstract:

    Using an animal model of drug relapse, we found that intermittent footshock stress reinstates alcohol seeking, an effect attenuated by the 5-HT reuptake blocker fluoxetine and by corticotropin-releasing factor (CRF) receptor antagonists. Here we studied the role of the 5-HT cell body region of the Median Raphe Nucleus (MRN) and CRF receptors in this site in reinstatement of alcohol seeking. Rats were given alcohol in a two-bottle choice procedure (water vs alcohol) for 25 d and were then trained for 1 hr/d to press a lever for alcohol (12% w/v) for 23–30 d. Subsequently, lever pressing for alcohol was extinguished by terminating drug delivery for 5–9 d. Tests for reinstatement of alcohol seeking were then performed under extinction conditions. Intra-MRN infusions of 8-OH-DPAT \[8-hydroxy-2-(di- n -propylamino)tetralin\] (a 5-HT1A agonist that decreases 5-HT cell firing and release) reinstated alcohol seeking. Reinstatement of alcohol seeking also was observed after intra-MRN infusions of low doses of CRF (3–10 ng), which mimicked the effect of ventricular infusions of higher doses of the peptide (300–1000 ng). Finally, intra-MRN infusions of the CRF receptor antagonist d -Phe CRF (50 ng) blocked the effect of intermittent footshock (10 min) on reinstatement. These data suggest that an interaction between CRF and 5-HT neurons within the MRN is involved in footshock stress-induced reinstatement of alcohol seeking.

A D Le - One of the best experts on this subject based on the ideXlab platform.

  • role of corticotropin releasing factor in the Median Raphe Nucleus in yohimbine induced reinstatement of alcohol seeking in rats
    Addiction Biology, 2013
    Co-Authors: A D Le, Douglas Funk, Kathleen M Coen, Zhaoxia Li, Yavin Shaham
    Abstract:

    The pharmacological stressor yohimbine increases ongoing alcohol self-administration and reinstates alcohol seeking in rats. This effect is attenuated by systemic injections of a corticotropin-releasing factor (CRF) antagonist. The brain sites involved in CRF's role in yohimbine-induced alcohol taking and seeking are unknown. We report that injections of the CRF receptor antagonist d-Phe CRF into the Median Raphe Nucleus (MRN) attenuated yohimbine-induced reinstatement of alcohol seeking but had no effect on yohimbine-induced increases in alcohol intake during ongoing self-administration. Results indicate an important role of MRN CRF receptors in yohimbine-induced reinstatement of alcohol seeking but not yohimbine-induced increases in alcohol intake.

  • effect of blockade of corticotropin releasing factor receptors in the Median Raphe Nucleus on stress induced c fos mrna in the rat brain
    Neuroscience, 2003
    Co-Authors: Douglas Funk, Zhaoxia Li, Yavin Shaham, A D Le
    Abstract:

    Using a rat relapse model, we have shown that infusion of a corticotropin-releasing factor (CRF) receptor antagonist into the Median Raphe Nucleus (MRN) blocks footshock stress-induced reinstatement of alcohol seeking in rats. The goal of the present study was to begin identifying brain sites potentially involved in this effect. For this purpose, we measured levels of c-fos mRNA in discrete nuclei of the rat brain following exposure to intermittent footshock, which was preceded by intra-MRN infusions of a CRF receptor antagonist, d-Phe CRF (0 or 50 ng). Exposure to intermittent footshock increased the expression of c-fos mRNA in a number of brain regions previously shown to be responsive to stressful stimuli. Pretreatment with d-Phe CRF in the MRN selectively attenuated the increases in c-fos mRNA induced by footshock in the central Nucleus of the amygdala (CeA). These findings are consistent with previous data on the important role for the CeA in stress-induced reinstatement of drug seeking. These results also suggest that inhibition of CeA activity may contribute to the blockade of alcohol-seeking induced by footshock that we have observed following injections of d-Phe into the MRN.

  • the role of corticotropin releasing factor in the Median Raphe Nucleus in relapse to alcohol
    The Journal of Neuroscience, 2002
    Co-Authors: A D Le, Stephen E Harding, W Juzytsch, Paul J Fletcher, Yavin Shaham
    Abstract:

    Using an animal model of drug relapse, we found that intermittent footshock stress reinstates alcohol seeking, an effect attenuated by the 5-HT reuptake blocker fluoxetine and by corticotropin-releasing factor (CRF) receptor antagonists. Here we studied the role of the 5-HT cell body region of the Median Raphe Nucleus (MRN) and CRF receptors in this site in reinstatement of alcohol seeking. Rats were given alcohol in a two-bottle choice procedure (water vs alcohol) for 25 d and were then trained for 1 hr/d to press a lever for alcohol (12% w/v) for 23–30 d. Subsequently, lever pressing for alcohol was extinguished by terminating drug delivery for 5–9 d. Tests for reinstatement of alcohol seeking were then performed under extinction conditions. Intra-MRN infusions of 8-OH-DPAT \[8-hydroxy-2-(di- n -propylamino)tetralin\] (a 5-HT1A agonist that decreases 5-HT cell firing and release) reinstated alcohol seeking. Reinstatement of alcohol seeking also was observed after intra-MRN infusions of low doses of CRF (3–10 ng), which mimicked the effect of ventricular infusions of higher doses of the peptide (300–1000 ng). Finally, intra-MRN infusions of the CRF receptor antagonist d -Phe CRF (50 ng) blocked the effect of intermittent footshock (10 min) on reinstatement. These data suggest that an interaction between CRF and 5-HT neurons within the MRN is involved in footshock stress-induced reinstatement of alcohol seeking.