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Hélio Zangrossi - One of the best experts on this subject based on the ideXlab platform.

  • Behavioral consequences of predator stress in the rat elevated T-Maze
    Physiology & behavior, 2015
    Co-Authors: Erika Mondin Bulos, Roger L H Pobbe, Hélio Zangrossi
    Abstract:

    Abstract Analyses of the behavioral reactions of rodents to predators have greatly contributed to the understanding of defense-related human psychopathologies such as anxiety and panic. We here investigated the behavioral consequences of exposing male Wistar rats to a live cat using the elevated T-Maze Test of anxiety. This Test allows the measurement of two defensive responses: inhibitory avoidance and escape, which in terms of pathology have been associated with generalized anxiety and panic disorders, respectively. For comparative reasons, the effects of exposure to the cat were also assessed in the elevated plus-maze. The results showed that a 5-min exposure to the cat selectively facilitated inhibitory avoidance acquisition, an anxiogenic effect, without affecting escape expression in the elevated T-Maze. This was seen immediately but not 30 min after contact with the predator. This short-lived anxiogenic effect was also detected in the elevated plus-maze. Previous administration of the benzodiazepine anxiolytic diazepam (2 mg/kg) decreased the immediate avoidance response to the predator and the neophobic reaction to a dummy cat used as a control stimulus. The drug also impaired inhibitory avoidance acquisition in the elevated T-Maze, indicating an anxiolytic effect, without affecting escape performance. The results indicate that the state of anxiety evoked during contact with the predator generalizes to both elevated plus- and T-Mazes, impacting on defensive responses associated with generalized anxiety disorder.

  • facilitation of 5 ht2a 2c mediated neurotransmission in the ventromedial hypothalamic nucleus decreases anxiety in the elevated t maze
    Behavioural Brain Research, 2011
    Co-Authors: Hélio Zangrossi, E S Da Silva, S C Poltronieri, Juliana Olivetti Guimaraes Nascimento, Milena De Barros Viana
    Abstract:

    Abstract Previous evidence has shown that facilitation of GABA/benzodiazepine-mediated neurotransmission in the ventromedial hypothalamus (VMH) inhibits both escape and inhibitory avoidance responses generated in the elevated T-Maze Test of anxiety (ETM). These defensive behaviors have been associated with panic and generalized anxiety, respectively. Aside from GABA/benzodiazepine receptors, the VMH also contains a significant number of serotonin (5-HT) receptors, including 1A, 2A and 2C subtypes. The purpose of the present study was to investigate the effect of the activation of 5-HT 1A and 5-HT 2A/2C receptors in the VMH on defensive behavioral responses in rats submitted to the ETM. For that, male Wistar rats were treated intra-VMH with the 5-HT 1A agonist 8-OH-DPAT, with the 5-HT 2A/2C agonist DOI, with the 5-HT 2C selective agonist MK-212, or with the 5-HT 2A/2C antagonist ketanserin and 10 min after were submitted to the ETM. Results showed that both DOI and MK-212 significantly decreased avoidance measurements, an anxiolytic-like effect, without altering escape. 8-OH-DPAT and ketanserin were without effect, although the last drug attenuated the effects of DOI. None of the drugs altered locomotor activity in an open field. These results suggest that 5-HT 2A/2C receptors of the VMH are involved in the regulation of inhibitory avoidance and might be of relevance to the physiopathology of generalized anxiety.

  • the lateral habenula regulates defensive behaviors through changes in 5 ht mediated neurotransmission in the dorsal periaqueductal gray matter
    Neuroscience Letters, 2010
    Co-Authors: Roger L H Pobbe, Hélio Zangrossi
    Abstract:

    Chemical stimulation of the lateral nucleus of the habenula (LHb), an area implicated in the regulation of serotonergic activity in raphe nuclei, affects the acquisition of inhibitory avoidance and escape expression of rats submitted to the elevated T-Maze Test of anxiety. Here, we investigated whether facilitation of 5-HT-mediated neurotransmission in the dorsal periaqueductal gray (dPAG) accounts for the behavioral consequences in the elevated T-Maze induced by chemical stimulation of the LHb. The dPAG in the midbrain, which is innervated by 5-HT fibers originating from the dorsal raphe nucleus (DRN), has been consistently implicated in the genesis/regulation of anxiety- and fear-related defensive responses. The results showed that intra-dPAG injection of WAY-100635 or ketanserin, 5-HT(1A) and 5-HT(2A/2C) receptor antagonists, respectively, counteracted the anti-escape effect caused by bilateral intra-LHb injection of kainic acid (60pmol/0.2microl). Ketanserin, but not WAY-100635, blocked kainic acid's facilitatory effect on inhibitory avoidance acquisition. Overall, the results suggest that the pathway connecting the LHb to the DRN is involved in the control of 5-HT release in the dPAG, and facilitation of 5-HT-mediated neurotransmission in the latter area distinctively impacts upon the expression of anxiety- and fear-related defensive behaviors. While stimulation of 5-HT(1A) receptors selectively affects escape performance, 5-HT(2A/2C) receptors modulate both inhibitory avoidance and escape.

  • involvement of median raphe nucleus 5 ht1a receptors in the regulation of generalized anxiety related defensive behaviours in rats
    Neuroscience Letters, 2008
    Co-Authors: Maria Adrielle Vicente, Carlos Eduardo Macedo, Lucineia Dos Santos, Hélio Zangrossi, Telma Goncalves Carneiro Spera De Andrade
    Abstract:

    Abstract Changes in 5-HT 1A receptor-mediated neurotransmission at the level of the median raphe nucleus (MRN) are reported to affect the expression of defensive responses that are associated with generalized anxiety disorder (e.g. inhibitory avoidance) but not with panic (e.g. escape). The objective of this study was to further explore the involvement of MRN 5-HT 1A receptors in the regulation of generalized anxiety-related behaviours. Results of experiment 1 showed that intra-MRN injection of the 5-HT 1A/7 receptor agonist 8-OH-DPAT (0.6 nmol) in male Wistar rats impaired the acquisition of inhibitory avoidance, without interfering with the performance of escape in the elevated T-Maze Test of anxiety. Pre-treatment with the 5-HT 1A receptor antagonist WAY-100635 (0.18 nmol) fully blocked this anxiolytic-like effect. As revealed by experiment 2, intra-MRN injection of 8-OH-DPAT (0.6, 3 or 15 nmol) also caused anxiolytic effect in rats submitted to the light–dark transition Test, another animal model that has been associated with generalized anxiety. In the same Test, intra-MRN injection of WAY-100635 (0.18, 0.37 or 0.74 nmol) caused the opposite effect. Overall, the current findings support the view that MRN 5-HT neurons, through the regulation of 5-HT 1A somatodendritic autoreceptors, are implicated in the regulation of generalized anxiety-associated behaviours.

  • 5 ht1a receptors in the dorsal hippocampus mediate the anxiogenic effect induced by the stimulation of 5 ht neurons in the median raphe nucleus
    European Neuropsychopharmacology, 2008
    Co-Authors: Lucineia Dos Santos, Telma Goncalves Carneiro Spera De Andrade, Hélio Zangrossi
    Abstract:

    Abstract We evaluated the involvement of dorsal hippocampus (DH) 5-HT 1A receptors in the mediation of the behavioral effects caused by the pharmacological manipulation of 5-HT neurons in the median raphe nucleus (MRN). To this end, we used the rat elevated T-Maze Test of anxiety. The results showed that intra-DH injection of the 5-HT 1A/7 agonist 8-OH-DPAT facilitated inhibitory avoidance, an anxiogenic effect, without affecting escape. Microinjection of the 5-HT 1A antagonist WAY-100635 was ineffective. In the elevated T-Maze, inhibitory avoidance and escape have been related to generalized anxiety and panic disorders, respectively. Intra-MRN administration of the excitatory aminoacid kainic acid, which non-selectively stimulates 5-HT neurons in this brain area facilitated inhibitory avoidance and impaired escape performance, but also affected locomotion. Intra-MRN injection of WAY-100635, which has a disinhibitory effect on the activity of 5-HT neurons in this midbrain area, only facilitated inhibitory avoidance. Pre-administration of WAY-100635 into the DH blocked the behavioral effect of intra-MRN injection of WAY-100635, but not of kainic acid. These results indicate that DH 5-HT 1A receptors mediate the anxiogenic effect induced by the selective stimulation of 5-HT neurons in the MRN.

Milena De Barros Viana - One of the best experts on this subject based on the ideXlab platform.

  • facilitation of 5 ht2a 2c mediated neurotransmission in the ventromedial hypothalamic nucleus decreases anxiety in the elevated t maze
    Behavioural Brain Research, 2011
    Co-Authors: Hélio Zangrossi, E S Da Silva, S C Poltronieri, Juliana Olivetti Guimaraes Nascimento, Milena De Barros Viana
    Abstract:

    Abstract Previous evidence has shown that facilitation of GABA/benzodiazepine-mediated neurotransmission in the ventromedial hypothalamus (VMH) inhibits both escape and inhibitory avoidance responses generated in the elevated T-Maze Test of anxiety (ETM). These defensive behaviors have been associated with panic and generalized anxiety, respectively. Aside from GABA/benzodiazepine receptors, the VMH also contains a significant number of serotonin (5-HT) receptors, including 1A, 2A and 2C subtypes. The purpose of the present study was to investigate the effect of the activation of 5-HT 1A and 5-HT 2A/2C receptors in the VMH on defensive behavioral responses in rats submitted to the ETM. For that, male Wistar rats were treated intra-VMH with the 5-HT 1A agonist 8-OH-DPAT, with the 5-HT 2A/2C agonist DOI, with the 5-HT 2C selective agonist MK-212, or with the 5-HT 2A/2C antagonist ketanserin and 10 min after were submitted to the ETM. Results showed that both DOI and MK-212 significantly decreased avoidance measurements, an anxiolytic-like effect, without altering escape. 8-OH-DPAT and ketanserin were without effect, although the last drug attenuated the effects of DOI. None of the drugs altered locomotor activity in an open field. These results suggest that 5-HT 2A/2C receptors of the VMH are involved in the regulation of inhibitory avoidance and might be of relevance to the physiopathology of generalized anxiety.

  • gaba benzodiazepine receptors in the ventromedial hypothalamic nucleus regulate both anxiety and panic related defensive responses in the elevated t maze
    Brain Research Bulletin, 2007
    Co-Authors: Hélio Zangrossi, Milena De Barros Viana, Cintia Bueno
    Abstract:

    Abstract It has been shown that facilitation of GABA-mediated neurotransmission in the medial nucleus of the amygdala and the dorsal periaqueductal gray (dPAG) inhibits the escape, but not the inhibitory avoidance response generated in the elevated T-Maze Test of anxiety (ETM). These defensive behaviors have been associated with panic and generalized anxiety, respectively. Previous evidence indicates that the dorsomedial part of the ventromedial hypothalamus (VMHdm), which is interconnected with these two brain areas, is also part of the neurobiological substrate controlling escape behavior. In the present study, we investigated in male Wistar rats whether the intra-VMHdm injection of GABA-modulating drugs differently affect the two defensive tasks measured in the ETM. The results showed that the microinjection of the benzodiazepine (BZD) receptor agonist midazolam (10, 20 and 40 nmol), the GABAA receptor agonist muscimol (2, 4 and 8 nmol) or the GABAB receptor agonist baclofen (2, 4 and 8 nmol) impaired inhibitory avoidance and escape performance, an anxiolytic and panicolytic-like effect, respectively. On the other hand, local administration of the BZD inverse agonist FG 7142 (20, 40 and 80 pmol) facilitated both behaviors, suggesting anxiogenic and panicogenic-like effects. These results were not due to motor alterations, since the drugs did not affect exploratory behavior in an open field. The data suggest that GABAA/BZD and GABAB receptors within the VMHdm are involved not only in the control of panic-related, but also of anxiety-related behaviors.

Telma Goncalves Carneiro Spera De Andrade - One of the best experts on this subject based on the ideXlab platform.

  • involvement of median raphe nucleus 5 ht1a receptors in the regulation of generalized anxiety related defensive behaviours in rats
    Neuroscience Letters, 2008
    Co-Authors: Maria Adrielle Vicente, Carlos Eduardo Macedo, Lucineia Dos Santos, Hélio Zangrossi, Telma Goncalves Carneiro Spera De Andrade
    Abstract:

    Abstract Changes in 5-HT 1A receptor-mediated neurotransmission at the level of the median raphe nucleus (MRN) are reported to affect the expression of defensive responses that are associated with generalized anxiety disorder (e.g. inhibitory avoidance) but not with panic (e.g. escape). The objective of this study was to further explore the involvement of MRN 5-HT 1A receptors in the regulation of generalized anxiety-related behaviours. Results of experiment 1 showed that intra-MRN injection of the 5-HT 1A/7 receptor agonist 8-OH-DPAT (0.6 nmol) in male Wistar rats impaired the acquisition of inhibitory avoidance, without interfering with the performance of escape in the elevated T-Maze Test of anxiety. Pre-treatment with the 5-HT 1A receptor antagonist WAY-100635 (0.18 nmol) fully blocked this anxiolytic-like effect. As revealed by experiment 2, intra-MRN injection of 8-OH-DPAT (0.6, 3 or 15 nmol) also caused anxiolytic effect in rats submitted to the light–dark transition Test, another animal model that has been associated with generalized anxiety. In the same Test, intra-MRN injection of WAY-100635 (0.18, 0.37 or 0.74 nmol) caused the opposite effect. Overall, the current findings support the view that MRN 5-HT neurons, through the regulation of 5-HT 1A somatodendritic autoreceptors, are implicated in the regulation of generalized anxiety-associated behaviours.

  • 5 ht1a receptors in the dorsal hippocampus mediate the anxiogenic effect induced by the stimulation of 5 ht neurons in the median raphe nucleus
    European Neuropsychopharmacology, 2008
    Co-Authors: Lucineia Dos Santos, Telma Goncalves Carneiro Spera De Andrade, Hélio Zangrossi
    Abstract:

    Abstract We evaluated the involvement of dorsal hippocampus (DH) 5-HT 1A receptors in the mediation of the behavioral effects caused by the pharmacological manipulation of 5-HT neurons in the median raphe nucleus (MRN). To this end, we used the rat elevated T-Maze Test of anxiety. The results showed that intra-DH injection of the 5-HT 1A/7 agonist 8-OH-DPAT facilitated inhibitory avoidance, an anxiogenic effect, without affecting escape. Microinjection of the 5-HT 1A antagonist WAY-100635 was ineffective. In the elevated T-Maze, inhibitory avoidance and escape have been related to generalized anxiety and panic disorders, respectively. Intra-MRN administration of the excitatory aminoacid kainic acid, which non-selectively stimulates 5-HT neurons in this brain area facilitated inhibitory avoidance and impaired escape performance, but also affected locomotion. Intra-MRN injection of WAY-100635, which has a disinhibitory effect on the activity of 5-HT neurons in this midbrain area, only facilitated inhibitory avoidance. Pre-administration of WAY-100635 into the DH blocked the behavioral effect of intra-MRN injection of WAY-100635, but not of kainic acid. These results indicate that DH 5-HT 1A receptors mediate the anxiogenic effect induced by the selective stimulation of 5-HT neurons in the MRN.

  • serotonergic neurons in the median raphe nucleus regulate inhibitory avoidance but not escape behavior in the rat elevated t maze Test of anxiety
    Psychopharmacology, 2005
    Co-Authors: Lucineia Dos Santos, Telma Goncalves Carneiro Spera De Andrade, Hélio Zangrossi
    Abstract:

    Rationale A wealth of evidence supports the involvement of the serotonergic neurons of the median raphe nucleus (MRN) in anxiety. However, it is presently unclear whether serotonergic pathways arising from this nucleus play distinguishing regulatory roles in defensive behaviors that have been associated with specific subtypes of anxiety disorders.

Lucineia Dos Santos - One of the best experts on this subject based on the ideXlab platform.

  • involvement of median raphe nucleus 5 ht1a receptors in the regulation of generalized anxiety related defensive behaviours in rats
    Neuroscience Letters, 2008
    Co-Authors: Maria Adrielle Vicente, Carlos Eduardo Macedo, Lucineia Dos Santos, Hélio Zangrossi, Telma Goncalves Carneiro Spera De Andrade
    Abstract:

    Abstract Changes in 5-HT 1A receptor-mediated neurotransmission at the level of the median raphe nucleus (MRN) are reported to affect the expression of defensive responses that are associated with generalized anxiety disorder (e.g. inhibitory avoidance) but not with panic (e.g. escape). The objective of this study was to further explore the involvement of MRN 5-HT 1A receptors in the regulation of generalized anxiety-related behaviours. Results of experiment 1 showed that intra-MRN injection of the 5-HT 1A/7 receptor agonist 8-OH-DPAT (0.6 nmol) in male Wistar rats impaired the acquisition of inhibitory avoidance, without interfering with the performance of escape in the elevated T-Maze Test of anxiety. Pre-treatment with the 5-HT 1A receptor antagonist WAY-100635 (0.18 nmol) fully blocked this anxiolytic-like effect. As revealed by experiment 2, intra-MRN injection of 8-OH-DPAT (0.6, 3 or 15 nmol) also caused anxiolytic effect in rats submitted to the light–dark transition Test, another animal model that has been associated with generalized anxiety. In the same Test, intra-MRN injection of WAY-100635 (0.18, 0.37 or 0.74 nmol) caused the opposite effect. Overall, the current findings support the view that MRN 5-HT neurons, through the regulation of 5-HT 1A somatodendritic autoreceptors, are implicated in the regulation of generalized anxiety-associated behaviours.

  • 5 ht1a receptors in the dorsal hippocampus mediate the anxiogenic effect induced by the stimulation of 5 ht neurons in the median raphe nucleus
    European Neuropsychopharmacology, 2008
    Co-Authors: Lucineia Dos Santos, Telma Goncalves Carneiro Spera De Andrade, Hélio Zangrossi
    Abstract:

    Abstract We evaluated the involvement of dorsal hippocampus (DH) 5-HT 1A receptors in the mediation of the behavioral effects caused by the pharmacological manipulation of 5-HT neurons in the median raphe nucleus (MRN). To this end, we used the rat elevated T-Maze Test of anxiety. The results showed that intra-DH injection of the 5-HT 1A/7 agonist 8-OH-DPAT facilitated inhibitory avoidance, an anxiogenic effect, without affecting escape. Microinjection of the 5-HT 1A antagonist WAY-100635 was ineffective. In the elevated T-Maze, inhibitory avoidance and escape have been related to generalized anxiety and panic disorders, respectively. Intra-MRN administration of the excitatory aminoacid kainic acid, which non-selectively stimulates 5-HT neurons in this brain area facilitated inhibitory avoidance and impaired escape performance, but also affected locomotion. Intra-MRN injection of WAY-100635, which has a disinhibitory effect on the activity of 5-HT neurons in this midbrain area, only facilitated inhibitory avoidance. Pre-administration of WAY-100635 into the DH blocked the behavioral effect of intra-MRN injection of WAY-100635, but not of kainic acid. These results indicate that DH 5-HT 1A receptors mediate the anxiogenic effect induced by the selective stimulation of 5-HT neurons in the MRN.

  • serotonergic neurons in the median raphe nucleus regulate inhibitory avoidance but not escape behavior in the rat elevated t maze Test of anxiety
    Psychopharmacology, 2005
    Co-Authors: Lucineia Dos Santos, Telma Goncalves Carneiro Spera De Andrade, Hélio Zangrossi
    Abstract:

    Rationale A wealth of evidence supports the involvement of the serotonergic neurons of the median raphe nucleus (MRN) in anxiety. However, it is presently unclear whether serotonergic pathways arising from this nucleus play distinguishing regulatory roles in defensive behaviors that have been associated with specific subtypes of anxiety disorders.

Tomoyuki Yoshida - One of the best experts on this subject based on the ideXlab platform.

  • il1rapl1 knockout mice show spine density decrease learning deficiency hyperactivity and reduced anxiety like behaviours
    Scientific Reports, 2015
    Co-Authors: Maya Yamazaki, Misato Yasumura, Kouta Kanno, Takeshi Uemura, Tomoyuki Yoshida, Rie Natsume, Keizo Takao
    Abstract:

    IL-1 receptor accessory protein-like 1 (IL1RAPL1) is responsible for nonsyndromic intellectual disability and is associated with autism. IL1RAPL1 mediates excitatory synapse formation through trans-synaptic interaction with PTPδ. Here, we showed that the spine density of cortical neurons was significantly reduced in IL1RAPL1 knockout mice. The spatial reference and working memories and remote fear memory were mildly impaired in IL1RAPL1 knockout mice. Furthermore, the behavioural flexibility was slightly reduced in the T-Maze Test. Interestingly, the performance of IL1RAPL1 knockout mice in the rotarod Test was significantly better than that of wild-type mice. Moreover, IL1RAPL1 knockout mice consistently exhibited high locomotor activity in all the tasks examined. In addition, open-space and height anxiety-like behaviours were decreased in IL1RAPL1 knockout mice. These results suggest that IL1RAPL1 ablation resulted in spine density decrease and affected not only learning but also behavioural flexibility, locomotor activity and anxiety.