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Marcus Lira Brandao - One of the best experts on this subject based on the ideXlab platform.

  • the benzodiazepine midazolam acts on the expression of the defensive behavior but not on the processing of aversive information produced by exposure to the elevated plus maze and electrical stimulations applied to the inferior colliculus of rats
    Neuropharmacology, 2015
    Co-Authors: Marcus Lira Brandao, Viviane M Saito
    Abstract:

    Abstract Electrical stimulation of Midbrain Tectum structures, particularly the dorsal periaqueductal gray (dPAG) and inferior colliculus (IC), produces defensive responses such as freezing and escape behavior. Freezing also results after termination of this stimulation (post-stimulation freezing; PSF). Whereas these responses are critically mediated by GABA in the dPAG, it is unclear how GABA-benzodiazepine mechanisms mediate the expression of fear (freezing and escape behaviors) and the processing of aversive information (PSF) produced by electrical stimulation of the IC. Since dorsal (ICd) and ventral regions (ICv) of the IC react differentially to aversive stimulation, we hypothesized that these regions might be sensitive to the action of benzodiazepine drugs when rats are submitted to animal models of anxiety: the elevated plus maze (EPM) and the IC electrical stimulation procedure. Midazolam (5, 10 or 20 nmol) was injected into the ICd or ICv of rats subjected to one of these tests. Intra-ICv, but not intra-ICd injections, of midazolam reduced the aversiveness of the IC electrical stimulation and decreased fear in the EPM, as assessed by its traditional and complementary measures. In contrast, the IC post-stimulation freezing remained unaltered with midazolam treatments. Thus, there is a clear pharmacological dissociation in the reactivity of dorsal and ventral regions of the IC to fear-provoking stimuli of the two animal models of anxiety used in this study. The present results support the proposal that benzodiazepine-mediated mechanisms are only involved in the output mechanisms of defensive behavior and not involved in the processing of ascending aversive information from the IC. This article is part of the Special Issue entitled ‘GABAergic Signaling in Health and Disease’.

  • involvement of Midbrain Tectum neurokinin mediated mechanisms in fear and anxiety
    Brazilian Journal of Medical and Biological Research, 2012
    Co-Authors: J C Brenes, A C Broiz, Gabriel Shimizu Bassi, Rainer K W Schwarting, Marcus Lira Brandao
    Abstract:

    Electrical stimulation of Midbrain Tectum structures, particularly the dorsal periaqueductal gray (dPAG) and inferior colliculus (IC), produces defensive responses, such as freezing and escape behavior. Freezing also ensues after termination of dPAG stimulation (post-stimulation freezing). These defensive reaction responses are critically mediated by γ-aminobutyric acid and 5-hydroxytryptamine mechanisms in the Midbrain Tectum. Neurokinins (NKs) also play a role in the mediation of dPAG stimulation-evoked fear, but how NK receptors are involved in the global processing and expression of fear at the level of the Midbrain Tectum is yet unclear. The present study investigated the role of NK-1 receptors in unconditioned defensive behavior induced by electrical stimulation of the dPAG and IC of male Wistar rats. Spantide (100 pmol/0.2 μL), a selective NK-1 antagonist, injected into these Midbrain structures had anti-aversive effects on defensive responses and distress ultrasonic vocalizations induced by stimulation of the dPAG but not of the IC. Moreover, intra-dPAG injections of spantide did not influence post-stimulation freezing or alter exploratory behavior in rats subjected to the elevated plus maze. These results suggest that NK-1 receptors are mainly involved in the mediation of defensive behavior organized in the dPAG. Dorsal periaqueductal gray-evoked post-stimulation freezing was not affected by intra-dPAG injections of spantide, suggesting that NK-1-mediated mechanisms are only involved in the output mechanisms of defensive behavior and not involved in the processing of ascending aversive information from the dPAG.

  • the unconditioned fear produced by morphine withdrawal is regulated by μ and κ opioid receptors in the Midbrain Tectum
    Behavioural Brain Research, 2009
    Co-Authors: Jana B De Ross, Marcus Lira Brandao, Milton A V Avila, Rafael N Ruggiero, Manoel Jorge Nobre, V M Castilho
    Abstract:

    We have recently shown that morphine withdrawal sensitizes the neural substrates of fear in the Midbrain Tectum structures--the dorsal periaqueductal gray (dPAG) and inferior colliculus (IC). In the present study, we investigated the role of mu- and kappa-opioid receptors in the mediation of these effects. Periadolescent rats chronically treated with morphine (10 mg/kg; s.c.) twice daily for 10 days were implanted with an electrode glued to a guide-cannula into the dPAG or the IC. Forty-eight hours after the interruption of this treatment, the effects of intra-dPAG or intra-IC microinjections of [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO; 0.6 and 1 nmol/0.2 microl)--a selective mu-receptor agonist--or nor-binaltorphimine (BNI; 2.5 and 5 microg/0.2 microl)--a selective kappa-receptor antagonist with tardive action--on the freezing and escape thresholds determined by electrical stimulation of the dPAG and the IC were examined. For both structures, morphine withdrawal produced pro-aversive effects. DAMGO and BNI had antiaversive effects when injected into the dPAG and IC of non-dependent rats. In morphine-withdrawn rats, only BNI continued to promote antiaversive effects in both structures. Whereas DAMGO lost its antiaversive efficacy when injected into the dPAG, only its highest dose promoted antiaversive effects in the IC of morphine-withdrawn rats, suggesting the development of an apparent tolerance. Thus, the enhanced reactivity of the Midbrain Tectum in morphine-withdrawn periadolescent rats may be due, at least partially, to an impairment of the inhibitory influence of mechanisms mediated by mu-receptors on the neural substrates of fear in this region.

  • involvement of the Midbrain Tectum in the unconditioned fear promoted by morphine withdrawal
    European Journal of Pharmacology, 2008
    Co-Authors: Marcus Lira Brandao, Milton A V Avila, Rafael N Ruggiero, Alicia Cabral, Manoel Jorge Nobre
    Abstract:

    The Midbrain Tectum structures, dorsal periaqueductal gray (dPAG) and inferior colliculus (IC), are involved in the organization of fear and anxiety states during the exposure to dangerous stimuli. Since opiate withdrawal is associated with increased anxiety in both humans and animals, this study aimed to investigate the possible sensitization of the neural substrates of fear in the Midbrain Tectum and its influence on the morphine withdrawal-induced anxiety. For the production of drug withdrawal, rats received morphine injections (10 mg/kg; s.c.) twice daily during 10 days. Forty-eight hours after the interruption of the chronic treatment, independent groups were probed in the elevated plus-maze and open-field tests. Additional groups of animals were implanted with a bipolar electrode into the dPAG or the IC and submitted to the electrical stimulation of these structures for the determination of the freezing and escape thresholds after 48 h of withdrawal. Our results showed that the morphine withdrawal promoted clear-cut levels of anxiety without the somatic signs of opiate withdrawal. Moreover, morphine-withdrawn rats had an increase in the reactivity to the electrical stimulation of the dPAG and the IC. These findings suggest that the increased anxiety induced by morphine withdrawal is associated with the sensitization of the neural substrates of fear in the dPAG and the IC. So, the present results give support to the hypothesis that withdrawal from chronic treatment with morphine leads to fear states possibly engendered by activation of the dPAG and IC, regardless of the production of somatic symptoms.

  • gabaergic regulation of the neural organization of fear in the Midbrain Tectum
    Neuroscience & Biobehavioral Reviews, 2005
    Co-Authors: Marcus Lira Brandao, Manoel Jorge Nobre, Karina Genaro Borelli, Julia Maria Dos Santos, Lucas Albrechetsouza, Amanda Ribeiro De Oliveira, Raquel Chacon Ruiz Martinez
    Abstract:

    In Midbrain Tectum (MT) structures, such as the dorsal periaqueductal gray (dPAG), the superior colliculus (SC) and the inferior colliculus (IC) GABAergic neurons exert a tonic control on the neural substrates involved in the expression of defensive reactions. In this review, we summarize behavioral, immunohistochemical (brain Fos distribution) and electrophysiological (auditory evoked potentials) data obtained with the reduction of GABA transmission by local injections of a GABA receptor blocker (bicuculline, BIC) or a glutamic acid decarboxylase inhibitor (semicarbazide, SMC) into the MT. Distinct patterns of Fos distribution were obtained following the freezing and escape reactions induced by MT injections of SMC and BIC, respectively. While only the laterodorsal nucleus of the thalamus was labeled after SMC-induced freezing, a widespread increase in Fos expression in the brain occurred after BIC-induced escape. Also, injections of SMC into the IC increased the auditory evoked potentials recorded from this structure. It is suggested that GABAergic mechanisms of MT are also called into play when sensory gating of the MT is activated during different emotional states.

Norberto Cysne Coimbra - One of the best experts on this subject based on the ideXlab platform.

  • dorsal raphe nucleus 5 hydroxytryptamine 2a receptors are critical for the organisation of panic attack like defensive behaviour and unconditioned fear induced antinociception elicited by the chemical stimulation of superior colliculus neurons
    European Neuropsychopharmacology, 2019
    Co-Authors: Raimundo Da Silva Soares, Rafael Carvalho Almada, Luiz Luciano Falconisobrinho, Norberto Cysne Coimbra
    Abstract:

    Abstract Microinjections of N-methyl- d -aspartic acid (NMDA) in the Midbrain Tectum structures produce panic attack-like defensive behaviours, followed by an antinociceptive response. It has been suggested that fear-related defensive responses organised by brainstem neurons can be modulated by 5-hydroxytryptamine (5-HT). However, there is a shortage of studies showing the role of dorsal raphe nucleus (DRN) 5-HT2A receptors in the modulation of panic-like behaviour and fear-induced antinociception organised by the superior colliculus (SC). The purpose of this study was to investigate the participation of DRN 5-HT2A receptors in the modulation of panic attack-like behaviour and antinociception evoked by intra-SC injections of NMDA. In experiment I, the animals received microinjections of physiological saline or NMDA (6, 9 and 12 nmol) in the deep layers of the SC (dlSC). In experiment II, the most effective dose of NMDA (12 nmol) or vehicle was preceded by microinjections of vehicle or the 5-HT2A receptor selective antagonist R-96544 at different concentrations (0.5, 5 and 10 nM) in the DRN. Both proaversive and antinociceptive effects elicited by intra-dlSC injections of NMDA were attenuated by DRN pretreatment with R-96544. In addition, a morphological analysis showed that 5-HT2A receptors are present in GABAergic interneurons in the DRN. Taken together, these findings suggest that DRN 5-HT2A receptors are critical for the modulation of both panic attack-like defensive behaviour organised by SC neurons and unconditioned fear-induced antinociception. A possible interaction between serotonergic inputs, GABAergic interneurons and serotonergic outputs from the DRN was also considered.

  • stimulation of the nigrotectal pathway at the level of the superior colliculus reduces threat recognition and causes a shift from avoidance to approach behavior
    Frontiers in Neural Circuits, 2018
    Co-Authors: Norberto Cysne Coimbra, Rafael Carvalho Almada, Andreas Genewsky, Daniel E Heinz, Paul M Kaplick, Carsten T Wotjak
    Abstract:

    Defensive behavioral responses are essential for survival in threating situations. The superior colliculus (SC) has been implicated in the generation of defensive behaviors elicited by visual, tactile, and auditory stimuli. Furthermore, substantia nigra pars reticulata (SNr) neurons are known to exert a modulatory effect on Midbrain Tectum neural substrates. However, the functional role of this nigrotectal pathway in threating situations is still poorly understood. Using optogenetics in freely behaving mice, we activated SNr projections at the level of the SC, and assessed consequences on behavioral performance in an open field test (OFT) and the beetle mania task (BMT). The latter confronts a mouse with an erratic moving robo-beetle and allows to measure active and passive defensive responses upon frequent encounter of the threatening object. Channelrhodopsin-2 (ChR2)-mediated activation of the inhibitory nigrotectal pathway did not affect anxiety-like and exploratory behavior in the OFT, but increased the number of contacts between robo-beetle and test mouse in the BMT. Depending on the size of the arena, active avoidance responses were reduced, whereas tolerance and close following of the robo-beetle were significantly increased. We conclude from the data that the nigrotectal pathway plays holds the potential to modulate innate fear by attenuating threat recognition and causing a shift from defensive to approach behavior.

  • chemical neuroanatomical and psychopharmacological evidence that κ receptor mediated endogenous opioid peptide neurotransmission in the dorsal and ventral mesencephalon modulates panic like behaviour
    European Journal of Pharmacology, 2013
    Co-Authors: Juliana Almeida Da Silva, G C D Eichenberger, Renato De Freitas, Claudia Maria Padovan, Norberto Cysne Coimbra
    Abstract:

    The chemical neuroanatomy and the effects of central administration of opioid antagonists on the innate fear-induced responses elicited by electrical (at escape behaviour threshold) stimulation of the Midbrain Tectum were determined. The aim of the present work was to investigate the interaction between the tecto-nigral endogenous opioid peptide-mediated disinhibitory pathways and nigro-tectal inhibitory links in the control of panic-like behaviour and their organisation in the continuum comprised by the deep layers of the superior colliculus (dlSC) and the dorsolateral columns of the periaqueductal grey matter (dlPAG). Beta-endorphin-labelled neurons and fibres were found in the dorsal Midbrain and also in the substantia nigra. Opioid varicose fibres and terminal buttons were widely distributed in PAG columns and in all substantia nigra subdivisions. Microinjections of naltrexone (a non-selective opioid receptor antagonist; 5.0 μg/0.2 μl) or nor-binaltorphimine (a selective κ-opioid receptor antagonist; 5.0 μg/0.2 μl) in the dlSC/dlPAG continuum, in independent groups of animals, induced significant increases in the escape thresholds for Midbrain Tectum electrical stimulation. The microinjection of naltrexone or nor-binaltorphimine into the SNpr also increased the escape behaviour threshold for electrical stimulation of dlSC/dlPAG. These morphological and neuropharmacological findings support previous evidence from our team for the role played by the interaction between opioidergic and GABAergic mechanisms in the modulation of innate fear-induced responses. The present data offer a neuroanatomical basis for both intratectal axo-axonic/pre-synaptic and tecto-nigral axo-somatic opioid inhibition of GABAergic nigro-tectal neurons that modulate the dorsal Midbrain neurons related to the organisation of fear-related emotional responses.

  • neuroanatomical approaches of the Tectum reticular pathways and immunohistochemical evidence for serotonin positive perikarya on neuronal substrates of the superior colliculus and periaqueductal gray matter involved in the elaboration of the defensiv
    Experimental Neurology, 2006
    Co-Authors: Norberto Cysne Coimbra, Karina Genaro Borelli, L A Da Silva, R De Oliveira, Renato Leonardo De Freitas, S J Ribeiro, Rodolfo C Pacagnella, J E Moreira
    Abstract:

    Abstract Deep layers of the superior colliculus, the dorsal periaqueductal gray matter and the inferior colliculus are Midbrain structures involved in the generation of defensive behavior and fear-induced anti-nociception. Local injections of the GABAA antagonist bicuculline into these structures have been used to produce this defense reaction. Serotonin is thought to be the main neurotransmitter to modulate such defense reaction in mammals. This study is the first attempt to employ immunohistochemical techniques to locate serotonergic cells in the same Midbrain sites from where defense reaction is evoked by chemical stimulation with bicuculline. The blockade of GABAA receptors in the neural substrates of the dorsal mesencephalon was followed by vigorous defensive reactions and increased nociceptive thresholds. Light microscopy immunocytochemistry with streptavidin method was used for the localization of the putative cells of defensive behavior with antibodies to serotonin in the rat's Midbrain. Neurons positive to serotonin were found in the Midbrain sites where defensive reactions were evoked by microinjection of bicuculline. Serotonin was localized to somata and projections of the neural networks of the mesencephalic Tectum. Immunohistochemical studies showed that the sites in which neuronal perikarya positive to serotonin were identified in intermediate and deep layers of the superior colliculus, and in the dorsal and ventral columns of the periaqueductal gray matter are the same which were activated during the generation of defense behaviors, such as alertness, freezing, and escape reactions, induced by bicuculline. These findings support the contention that serotonin and GABAergic neurons may act in concert in the modulation of defense reaction in the Midbrain Tectum. Our neuroanatomical findings indicate a direct neural pathway connecting the dorsal Midbrain and monoaminergic nuclei of the descending pain inhibitory system, with profuse synaptic terminals mainly in the pontine reticular formation, gigantocellularis nucleus, and nucleus raphe magnus. The Midbrain Tectum-gigantocellularis complex and Midbrain Tectum-nucleus raphe magnus neural pathways may provide an alternative output allowing the organization of the fear-induced anti-nociception by mesencephalic networks.

  • neuroanatomical and psychopharmacological evidence for interaction between opioid and gabaergic neural pathways in the modulation of fear and defense elicited by electrical and chemical stimulation of the deep layers of the superior colliculus and dorsal periaqueductal gray matter
    Neuropharmacology, 2002
    Co-Authors: G C D Eichenberger, M Y Osaki, Sandro Jose Ribeiro, R Y Maruoka, G C C Resende, Lissandra Castellanbaldan, Sonia A L Correa, L A Da Silva, Norberto Cysne Coimbra
    Abstract:

    The effects of central administration of opioid antagonists on the aversive responses elicited by electrical (at the freezing and escape thresholds) or chemical stimulation (crossings, rearings, turnings and jumps, induced by microinjections of bicuculline) of the Midbrain Tectum were determined. Central microinjections of naloxone and naltrexone in the mesencephalic Tectum caused a significant increase in the freezing and escape thresholds elicited by electrical Midbrain Tectum stimulation. Furthermore, both opioid antagonists caused a significant decrease in the mean incidence of aversive behavioral responses induced by microinjections of bicuculline in the deep layers of the superior colliculus (DLSC) and in dorsal aspects of the periaqueductal gray matter (DPAG), as compared with controls. These findings suggest an opioid modulation of the GABAergic inhibitory inputs controlling the aversive behavior elicited by Midbrain Tectum stimulation. In fact, immunohistochemical evidence suggests that the dorsal mesencephalon is rich in β-endorphin-containing neurons and fibers with varicosities. Iontophoretical microinjections of the neurotracer biodextran in the substantia nigra, pars reticulata (SNpr), show nigro-tectal pathways connecting SNpr with the same neural substrate of the DPAG rich in neuronal cells immunoreactive for opioid peptides. Labeled neurons of the DLSC and periaqueductal gray matter send inputs with varsicosities to ipsi- and contralateral DPAG and ipsilateral SNpr. These findings, in addition to the psychopharmacological evidence for the interaction between opioid and GABAergic mechanisms, offer a neuroanatomical basis of a possible presynaptic opioid inhibition of GABAergic nigro-tectal neurons modulating the fear in aversive structures of the cranial mesencephalon, in a short link, and maybe through a major neural circuit, also in GABA-containing perikarya of nigro-tectal neurons.

Manoel Jorge Nobre - One of the best experts on this subject based on the ideXlab platform.

  • the unconditioned fear produced by morphine withdrawal is regulated by μ and κ opioid receptors in the Midbrain Tectum
    Behavioural Brain Research, 2009
    Co-Authors: Jana B De Ross, Marcus Lira Brandao, Milton A V Avila, Rafael N Ruggiero, Manoel Jorge Nobre, V M Castilho
    Abstract:

    We have recently shown that morphine withdrawal sensitizes the neural substrates of fear in the Midbrain Tectum structures--the dorsal periaqueductal gray (dPAG) and inferior colliculus (IC). In the present study, we investigated the role of mu- and kappa-opioid receptors in the mediation of these effects. Periadolescent rats chronically treated with morphine (10 mg/kg; s.c.) twice daily for 10 days were implanted with an electrode glued to a guide-cannula into the dPAG or the IC. Forty-eight hours after the interruption of this treatment, the effects of intra-dPAG or intra-IC microinjections of [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO; 0.6 and 1 nmol/0.2 microl)--a selective mu-receptor agonist--or nor-binaltorphimine (BNI; 2.5 and 5 microg/0.2 microl)--a selective kappa-receptor antagonist with tardive action--on the freezing and escape thresholds determined by electrical stimulation of the dPAG and the IC were examined. For both structures, morphine withdrawal produced pro-aversive effects. DAMGO and BNI had antiaversive effects when injected into the dPAG and IC of non-dependent rats. In morphine-withdrawn rats, only BNI continued to promote antiaversive effects in both structures. Whereas DAMGO lost its antiaversive efficacy when injected into the dPAG, only its highest dose promoted antiaversive effects in the IC of morphine-withdrawn rats, suggesting the development of an apparent tolerance. Thus, the enhanced reactivity of the Midbrain Tectum in morphine-withdrawn periadolescent rats may be due, at least partially, to an impairment of the inhibitory influence of mechanisms mediated by mu-receptors on the neural substrates of fear in this region.

  • involvement of the Midbrain Tectum in the unconditioned fear promoted by morphine withdrawal
    European Journal of Pharmacology, 2008
    Co-Authors: Marcus Lira Brandao, Milton A V Avila, Rafael N Ruggiero, Alicia Cabral, Manoel Jorge Nobre
    Abstract:

    The Midbrain Tectum structures, dorsal periaqueductal gray (dPAG) and inferior colliculus (IC), are involved in the organization of fear and anxiety states during the exposure to dangerous stimuli. Since opiate withdrawal is associated with increased anxiety in both humans and animals, this study aimed to investigate the possible sensitization of the neural substrates of fear in the Midbrain Tectum and its influence on the morphine withdrawal-induced anxiety. For the production of drug withdrawal, rats received morphine injections (10 mg/kg; s.c.) twice daily during 10 days. Forty-eight hours after the interruption of the chronic treatment, independent groups were probed in the elevated plus-maze and open-field tests. Additional groups of animals were implanted with a bipolar electrode into the dPAG or the IC and submitted to the electrical stimulation of these structures for the determination of the freezing and escape thresholds after 48 h of withdrawal. Our results showed that the morphine withdrawal promoted clear-cut levels of anxiety without the somatic signs of opiate withdrawal. Moreover, morphine-withdrawn rats had an increase in the reactivity to the electrical stimulation of the dPAG and the IC. These findings suggest that the increased anxiety induced by morphine withdrawal is associated with the sensitization of the neural substrates of fear in the dPAG and the IC. So, the present results give support to the hypothesis that withdrawal from chronic treatment with morphine leads to fear states possibly engendered by activation of the dPAG and IC, regardless of the production of somatic symptoms.

  • gabaergic regulation of the neural organization of fear in the Midbrain Tectum
    Neuroscience & Biobehavioral Reviews, 2005
    Co-Authors: Marcus Lira Brandao, Manoel Jorge Nobre, Karina Genaro Borelli, Julia Maria Dos Santos, Lucas Albrechetsouza, Amanda Ribeiro De Oliveira, Raquel Chacon Ruiz Martinez
    Abstract:

    In Midbrain Tectum (MT) structures, such as the dorsal periaqueductal gray (dPAG), the superior colliculus (SC) and the inferior colliculus (IC) GABAergic neurons exert a tonic control on the neural substrates involved in the expression of defensive reactions. In this review, we summarize behavioral, immunohistochemical (brain Fos distribution) and electrophysiological (auditory evoked potentials) data obtained with the reduction of GABA transmission by local injections of a GABA receptor blocker (bicuculline, BIC) or a glutamic acid decarboxylase inhibitor (semicarbazide, SMC) into the MT. Distinct patterns of Fos distribution were obtained following the freezing and escape reactions induced by MT injections of SMC and BIC, respectively. While only the laterodorsal nucleus of the thalamus was labeled after SMC-induced freezing, a widespread increase in Fos expression in the brain occurred after BIC-induced escape. Also, injections of SMC into the IC increased the auditory evoked potentials recorded from this structure. It is suggested that GABAergic mechanisms of MT are also called into play when sensory gating of the MT is activated during different emotional states.

L A Da Silva - One of the best experts on this subject based on the ideXlab platform.

  • neuroanatomical approaches of the Tectum reticular pathways and immunohistochemical evidence for serotonin positive perikarya on neuronal substrates of the superior colliculus and periaqueductal gray matter involved in the elaboration of the defensiv
    Experimental Neurology, 2006
    Co-Authors: Norberto Cysne Coimbra, Karina Genaro Borelli, L A Da Silva, R De Oliveira, Renato Leonardo De Freitas, S J Ribeiro, Rodolfo C Pacagnella, J E Moreira
    Abstract:

    Abstract Deep layers of the superior colliculus, the dorsal periaqueductal gray matter and the inferior colliculus are Midbrain structures involved in the generation of defensive behavior and fear-induced anti-nociception. Local injections of the GABAA antagonist bicuculline into these structures have been used to produce this defense reaction. Serotonin is thought to be the main neurotransmitter to modulate such defense reaction in mammals. This study is the first attempt to employ immunohistochemical techniques to locate serotonergic cells in the same Midbrain sites from where defense reaction is evoked by chemical stimulation with bicuculline. The blockade of GABAA receptors in the neural substrates of the dorsal mesencephalon was followed by vigorous defensive reactions and increased nociceptive thresholds. Light microscopy immunocytochemistry with streptavidin method was used for the localization of the putative cells of defensive behavior with antibodies to serotonin in the rat's Midbrain. Neurons positive to serotonin were found in the Midbrain sites where defensive reactions were evoked by microinjection of bicuculline. Serotonin was localized to somata and projections of the neural networks of the mesencephalic Tectum. Immunohistochemical studies showed that the sites in which neuronal perikarya positive to serotonin were identified in intermediate and deep layers of the superior colliculus, and in the dorsal and ventral columns of the periaqueductal gray matter are the same which were activated during the generation of defense behaviors, such as alertness, freezing, and escape reactions, induced by bicuculline. These findings support the contention that serotonin and GABAergic neurons may act in concert in the modulation of defense reaction in the Midbrain Tectum. Our neuroanatomical findings indicate a direct neural pathway connecting the dorsal Midbrain and monoaminergic nuclei of the descending pain inhibitory system, with profuse synaptic terminals mainly in the pontine reticular formation, gigantocellularis nucleus, and nucleus raphe magnus. The Midbrain Tectum-gigantocellularis complex and Midbrain Tectum-nucleus raphe magnus neural pathways may provide an alternative output allowing the organization of the fear-induced anti-nociception by mesencephalic networks.

  • neuroanatomical and psychopharmacological evidence for interaction between opioid and gabaergic neural pathways in the modulation of fear and defense elicited by electrical and chemical stimulation of the deep layers of the superior colliculus and dorsal periaqueductal gray matter
    Neuropharmacology, 2002
    Co-Authors: G C D Eichenberger, M Y Osaki, Sandro Jose Ribeiro, R Y Maruoka, G C C Resende, Lissandra Castellanbaldan, Sonia A L Correa, L A Da Silva, Norberto Cysne Coimbra
    Abstract:

    The effects of central administration of opioid antagonists on the aversive responses elicited by electrical (at the freezing and escape thresholds) or chemical stimulation (crossings, rearings, turnings and jumps, induced by microinjections of bicuculline) of the Midbrain Tectum were determined. Central microinjections of naloxone and naltrexone in the mesencephalic Tectum caused a significant increase in the freezing and escape thresholds elicited by electrical Midbrain Tectum stimulation. Furthermore, both opioid antagonists caused a significant decrease in the mean incidence of aversive behavioral responses induced by microinjections of bicuculline in the deep layers of the superior colliculus (DLSC) and in dorsal aspects of the periaqueductal gray matter (DPAG), as compared with controls. These findings suggest an opioid modulation of the GABAergic inhibitory inputs controlling the aversive behavior elicited by Midbrain Tectum stimulation. In fact, immunohistochemical evidence suggests that the dorsal mesencephalon is rich in β-endorphin-containing neurons and fibers with varicosities. Iontophoretical microinjections of the neurotracer biodextran in the substantia nigra, pars reticulata (SNpr), show nigro-tectal pathways connecting SNpr with the same neural substrate of the DPAG rich in neuronal cells immunoreactive for opioid peptides. Labeled neurons of the DLSC and periaqueductal gray matter send inputs with varsicosities to ipsi- and contralateral DPAG and ipsilateral SNpr. These findings, in addition to the psychopharmacological evidence for the interaction between opioid and GABAergic mechanisms, offer a neuroanatomical basis of a possible presynaptic opioid inhibition of GABAergic nigro-tectal neurons modulating the fear in aversive structures of the cranial mesencephalon, in a short link, and maybe through a major neural circuit, also in GABA-containing perikarya of nigro-tectal neurons.

G C D Eichenberger - One of the best experts on this subject based on the ideXlab platform.

  • chemical neuroanatomical and psychopharmacological evidence that κ receptor mediated endogenous opioid peptide neurotransmission in the dorsal and ventral mesencephalon modulates panic like behaviour
    European Journal of Pharmacology, 2013
    Co-Authors: Juliana Almeida Da Silva, G C D Eichenberger, Renato De Freitas, Claudia Maria Padovan, Norberto Cysne Coimbra
    Abstract:

    The chemical neuroanatomy and the effects of central administration of opioid antagonists on the innate fear-induced responses elicited by electrical (at escape behaviour threshold) stimulation of the Midbrain Tectum were determined. The aim of the present work was to investigate the interaction between the tecto-nigral endogenous opioid peptide-mediated disinhibitory pathways and nigro-tectal inhibitory links in the control of panic-like behaviour and their organisation in the continuum comprised by the deep layers of the superior colliculus (dlSC) and the dorsolateral columns of the periaqueductal grey matter (dlPAG). Beta-endorphin-labelled neurons and fibres were found in the dorsal Midbrain and also in the substantia nigra. Opioid varicose fibres and terminal buttons were widely distributed in PAG columns and in all substantia nigra subdivisions. Microinjections of naltrexone (a non-selective opioid receptor antagonist; 5.0 μg/0.2 μl) or nor-binaltorphimine (a selective κ-opioid receptor antagonist; 5.0 μg/0.2 μl) in the dlSC/dlPAG continuum, in independent groups of animals, induced significant increases in the escape thresholds for Midbrain Tectum electrical stimulation. The microinjection of naltrexone or nor-binaltorphimine into the SNpr also increased the escape behaviour threshold for electrical stimulation of dlSC/dlPAG. These morphological and neuropharmacological findings support previous evidence from our team for the role played by the interaction between opioidergic and GABAergic mechanisms in the modulation of innate fear-induced responses. The present data offer a neuroanatomical basis for both intratectal axo-axonic/pre-synaptic and tecto-nigral axo-somatic opioid inhibition of GABAergic nigro-tectal neurons that modulate the dorsal Midbrain neurons related to the organisation of fear-related emotional responses.

  • neuroanatomical and psychopharmacological evidence for interaction between opioid and gabaergic neural pathways in the modulation of fear and defense elicited by electrical and chemical stimulation of the deep layers of the superior colliculus and dorsal periaqueductal gray matter
    Neuropharmacology, 2002
    Co-Authors: G C D Eichenberger, M Y Osaki, Sandro Jose Ribeiro, R Y Maruoka, G C C Resende, Lissandra Castellanbaldan, Sonia A L Correa, L A Da Silva, Norberto Cysne Coimbra
    Abstract:

    The effects of central administration of opioid antagonists on the aversive responses elicited by electrical (at the freezing and escape thresholds) or chemical stimulation (crossings, rearings, turnings and jumps, induced by microinjections of bicuculline) of the Midbrain Tectum were determined. Central microinjections of naloxone and naltrexone in the mesencephalic Tectum caused a significant increase in the freezing and escape thresholds elicited by electrical Midbrain Tectum stimulation. Furthermore, both opioid antagonists caused a significant decrease in the mean incidence of aversive behavioral responses induced by microinjections of bicuculline in the deep layers of the superior colliculus (DLSC) and in dorsal aspects of the periaqueductal gray matter (DPAG), as compared with controls. These findings suggest an opioid modulation of the GABAergic inhibitory inputs controlling the aversive behavior elicited by Midbrain Tectum stimulation. In fact, immunohistochemical evidence suggests that the dorsal mesencephalon is rich in β-endorphin-containing neurons and fibers with varicosities. Iontophoretical microinjections of the neurotracer biodextran in the substantia nigra, pars reticulata (SNpr), show nigro-tectal pathways connecting SNpr with the same neural substrate of the DPAG rich in neuronal cells immunoreactive for opioid peptides. Labeled neurons of the DLSC and periaqueductal gray matter send inputs with varsicosities to ipsi- and contralateral DPAG and ipsilateral SNpr. These findings, in addition to the psychopharmacological evidence for the interaction between opioid and GABAergic mechanisms, offer a neuroanatomical basis of a possible presynaptic opioid inhibition of GABAergic nigro-tectal neurons modulating the fear in aversive structures of the cranial mesencephalon, in a short link, and maybe through a major neural circuit, also in GABA-containing perikarya of nigro-tectal neurons.

  • effects of opioid receptor blockade on defensive behavior elicited by electrical stimulation of the aversive substrates of the inferior colliculus in rattus norvegicus rodentia muridae
    Psychopharmacology, 2000
    Co-Authors: Norberto Cysne Coimbra, M Y Osaki, G C D Eichenberger, J G Ciscato, C E B Juca, C R Biojone
    Abstract:

    Rationale: Electrical or chemical stimulation of some structures of the Midbrain Tectum, such as the dorsal periaqueductal gray matter, deep layers of the superior colliculus and inferior colliculus induce fear and flight behavior. These structures constitute the main neural substrates commanding defensive behavior in brainstem. Many neurotransmitters are implicated in the modulation of aversion at the mesencephalic level. Objective: The aim of this work is to investigate the involvement of opioid mechanisms in modulation of defensive behavior in dorsal mesencephalon. Methods: Male Wistar rats were fixed in a stereotaxic frame and a chemitrode was implanted into the Midbrain, targeted to the central nucleus of the inferior colliculus. In the present study, the effects of peripheral and central administration of naloxone, naltrexone or naloxonazine on aversive thresholds (freezing and escape reactions) elicited by electrical stimulation of the Midbrain Tectum were determined. Results: Peripherally and centrally administered naloxone caused a significant increase in the freezing and flight thresholds elicited by electrical stimulation of the aversive substrates of the inferior colliculus. These effects were confirmed by peripheral and central administration of naltrexone and by microinjections of naloxonazine in inferior colliculus. Conclusions: These findings suggest that endogenous opioids are involved in the modulation of the aversive behavior elicited by Midbrain Tectum stimulation. Since microinjections of naloxonazine in the central nucleus of the inferior colliculus caused a significant increase in the aversive thresholds elicited by electrical stimulation of this structure, it is possible that µ1-opioid receptor located in this nucleus may be critically implicated in this neural circuitry.