Pharmacological evidence for the mediation of the panicolytic effect of fluoxetine by dorsal periaqueductal gray matter μ-opioid receptors

Roncon, Camila Marroni; Almada, Rafael Carvalho; Maraschin, Jhonatan Christian; Audi, Elisabeth Aparecida; Zangrossi, Hélio; Graeff, Frederico Guilherme; Coimbra, Norberto Cysne

doi:10.1016/j.neuropharm.2015.08.037

Cited by 21 publications

(10 citation statements)

References 35 publications

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“…Interestingly, depending on the dose and site of microinjections, both selective µ-opioid receptor agonists at low doses and µ-opioid receptor antagonists at higher doses cause panicolytic-like effects (Da Silva et al, 2017). Indeed, there is a controversy in the literature concerning the pro-aversive and/or anti-aversive effects of opioid agonists and antagonists, and there are different hypotheses to explain these apparently paradoxical findings, either suggesting that the pro-aversive effect of intracollicular morphine is due to its action on µ-opioid receptors and its pro-aversive effect is a consequence of its action on κ-opioid receptors (Cardoso et al, 1992;Nobre et al, 2000) or suggesting that the anti-aversive effects of opioid agonists are due to a cooperation between endogenous opioid neuropeptides and serotonin (Roncon et al, 2013(Roncon et al, , 2015(Roncon et al, , 2017. However, our team has consistently supported the hypothesis of the interaction among disinhibitory pre-synaptic endogenous opioid peptide signalling inputs to nigro-tectal GABAergic inhibitory projections (Castellan-Baldan et al, 2006;Eichenberger et al, 2002;Ribeiro et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Panicolytic-like effect of µ₁-opioid receptor blockade in the inferior colliculus of prey threatened by Crotalus durissus terrificus pit vipers

et al. 2019

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Background: The endogenous opioid peptide system has been implicated in the neural modulation of fear and anxiety organised by the dorsal midbrain. Furthermore, previous results indicate a fundamental role played by inferior colliculus (IC) opioid mechanisms during the expression of defensive behaviours, but the involvement of the IC µ1-opioid receptor in the modulation of anxiety- and panic attack-related behaviours remains unclear. Using a prey-versus-snake confrontation paradigm, we sought to investigate the effects of µ1-opioid receptor blockade in the IC on the defensive behaviour displayed by rats in a dangerous situation. Methods: Specific pathogen-free Wistar rats were treated with microinjection of the selective µ1-opioid receptor antagonist naloxonazine into the IC at different concentrations (1.0, 3.0 and 5.0 µg/0.2 µL) and then confronted with rattlesnakes (Crotalus durissus terrificus). The defensive behavioural repertoire, such as defensive attention, flat back approach (FBA), startle, defensive immobility, escape or active avoidance, displayed by rats either during the confrontations with wild snakes or during re-exposure to the experimental context without the predator was analysed. Results: The blockade of µ1-opioid receptors in the IC decreased the expression of both anxiety-related behaviours (defensive attention, FBA) and panic attack-related responses (startle, defensive immobility and escape) during the confrontation with rattlesnakes. A significant decrease in defensive attention was also recorded during re-exposure of the prey to the experimental apparatus context without the predator. Conclusion: Taken together, these results suggest that a decrease in µ1-opioid receptor signalling activity within the IC modulates anxiety- and panic attack-related behaviours in dangerous environments.

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Section: Discussionmentioning

confidence: 99%

Panicolytic-like effect of µ₁-opioid receptor blockade in the inferior colliculus of prey threatened by Crotalus durissus terrificus pit vipers

et al. 2019

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“…The neuropharmacological bases of those actions could be the following: (a) modulation of GABAergic inputs to the IC that can be mediated through striato-nigral disinhibitory projections (Almada and Coimbra, 2015) and (b) direct opioid-serotoninergic receptor interactions in terminals of the nigro-collicular pathways on the IC neural substrates. In fact, modulatory interactions between µ-opioid and GABAergic projections (Castellan-Baldan et al, 2006; Ribeiro et al, 2005), and also between µ-opioid and serotoninergic receptors (Roncon et al, 2013, 2015; Vaughan et al, 1997) were consistently described as occurring in the midbrain. In addition, GABAergic and serotonergic receptor interactions should be also considered during the modulation of the dorsal midbrain neuronal network related to innate fear-related responses.…”

Section: Discussionmentioning

confidence: 99%

The endogenous opioid system modulates defensive behavior evoked by Crotalus durissus terrificus: Panicolytic-like effect of intracollicular non-selective opioid receptors blockade

et al. 2018

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Background: There is a controversy regarding the key role played by opioid peptide neurotransmission in the modulation of panic-attack-related responses. Aims: Using a prey versus rattlesnakes paradigm, the present work investigated the involvement of the endogenous opioid peptide-mediated system of the inferior colliculus in the modulation of panic attack-related responses. Methods: Wistar rats were pretreated with intracollicular administration of either physiological saline or naloxone at different concentrations and confronted with rattlesnakes (Crotalus durissus terrificus). The prey versus rattlesnake confrontations were performed in a polygonal arena for snakes. The defensive behaviors displayed by prey (defensive attention, defensive immobility, escape response, flat back approach and startle) were recorded twice: firstly, over a period of 15 min the presence of the predator and a re-exposure was performed 24 h after the confrontation, when animals were exposed to the experimental enclosure without the rattlesnake. Results: The intramesencephalic non-specific blockade of opioid receptors with microinjections of naloxone at higher doses decreased both anxiety- (defensive attention and flat back approach) and panic attack-like (defensive immobility and escape) behaviors, evoked in the presence of rattlesnakes and increased non-defensive responses. During the exposure to the experimental context, there was a decrease in duration of defensive attention. Conclusions: These findings suggest a panicolytic-like effect of endogenous opioid receptors antagonism in the inferior colliculus on innate (panic attack) and conditioned (anticipatory anxiety) fear in rats threatened by rattlesnakes.

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“…Unconditioned fear-related studies have aimed to investigate the role of the dPAG in fear-related behavior (Brandão et al, 1999(Brandão et al, , 2005Castilho and Brandão, 2001;Roncon et al, 2015;Twardowschy and Coimbra, 2015). Several studies have indicated anti-aversive effects of DA in the midbrain tectum, with emphasis on the dPAG, deep layers of the superior colliculus (dlSC), and inferior colliculus (Brandão et al, 2015;Brandão and Coimbra, 2019;De Oliveira et al, 2014;Muthuraju et al, 2014)).…”

Section: In-da Applicationmentioning

confidence: 99%

Intranasal dopamine attenuates fear responses induced by electric shock to the foot and by electrical stimulation of the dorsal periaqueductal gray matter

et al. 2019

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Purpose: Intranasally applied dopamine (IN-DA), which likely reaches the brain via nasal–brain pathways and bypasses the blood–brain barrier, has been found to increase extracellular DA and bind to the DA2 transporter in the striatum. Recent studies suggest that DA plays a significant role in the processing of signaled and unconditioned aversive stimulation, including evidence that may attenuate responses to painful input. The purpose of this study was to examine the effects of IN-DA on fear-related behaviors induced by electric shock to the foot or by electrical stimulation of the dorsal periaqueductal gray matter (dPAG). Methods: DA hydrochloride suspended in a viscous castor oil gel (1 or 2 mg/kg) was applied (IN-DA) in a volume of 5 μL into the nostrils of adult Wistar male rats in order to evaluate its effects on (a) freezing induced by electric shock to the foot and (b) thresholds of freezing and escape and duration of post-stimulation freezing induced by electrical stimulation of the dPAG. Results: IN-DA attenuated freezing induced by electric shock to the foot in the three test trials, indicating that it reduced long-term fear responses. IN-DA also increased the threshold of dPAG stimulation-induced escape responses and reduced post-stimulation freezing. Conclusions: IN-DA, which has previously been shown to facilitate learning and to have antidepressive-like effects, attenuated unconditioned fear responses elicited by peripheral and intramesencephalic (dPAG) stimulation and reduced long-term conditioned fear responses.

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Pharmacological evidence for the mediation of the panicolytic effect of fluoxetine by dorsal periaqueductal gray matter μ-opioid receptors

Cited by 21 publications

References 35 publications

Panicolytic-like effect of µ₁-opioid receptor blockade in the inferior colliculus of prey threatened by Crotalus durissus terrificus pit vipers

Panicolytic-like effect of µ₁-opioid receptor blockade in the inferior colliculus of prey threatened by Crotalus durissus terrificus pit vipers

The endogenous opioid system modulates defensive behavior evoked by Crotalus durissus terrificus: Panicolytic-like effect of intracollicular non-selective opioid receptors blockade

Intranasal dopamine attenuates fear responses induced by electric shock to the foot and by electrical stimulation of the dorsal periaqueductal gray matter

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Pharmacological evidence for the mediation of the panicolytic effect of fluoxetine by dorsal periaqueductal gray matter μ-opioid receptors

Cited by 21 publications

References 35 publications

Panicolytic-like effect of µ1-opioid receptor blockade in the inferior colliculus of prey threatened by Crotalus durissus terrificus pit vipers

Panicolytic-like effect of µ1-opioid receptor blockade in the inferior colliculus of prey threatened by Crotalus durissus terrificus pit vipers

The endogenous opioid system modulates defensive behavior evoked by Crotalus durissus terrificus: Panicolytic-like effect of intracollicular non-selective opioid receptors blockade

Intranasal dopamine attenuates fear responses induced by electric shock to the foot and by electrical stimulation of the dorsal periaqueductal gray matter

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Panicolytic-like effect of µ₁-opioid receptor blockade in the inferior colliculus of prey threatened by Crotalus durissus terrificus pit vipers

Panicolytic-like effect of µ₁-opioid receptor blockade in the inferior colliculus of prey threatened by Crotalus durissus terrificus pit vipers