D₂-like receptor activation by intranasal dopamine attenuates fear responses induced by electrical stimulation of the dorsal periaqueductal grey matter, but fails to reduce aversion to pit vipers and T-maze performance

Abstract

Background: Panic-like reactions elicited by electrical stimulation of the dorsal periaqueductal grey matter (ES-dPAG) seem to be regulated by dopamine (DA). We showed that DA applied intranasally (IN) increased escape-behaviour thresholds induced by ES-dPAG of rats, indicating a panicolytic-like effect. Aims: We investigated whether IN-DA increases escape-response thresholds induced by ES-dPAG by acting on D2-like receptors, and whether IN-DA affects escape responses elicited by the presence of a potential predator and by open space and height of the elevated T-maze (ETM) as well as motor performance in the open field (OF) test. Methods: Wistar rats exposed to ES-dPAG were treated with Sulpiride (SUL, 40 mg/kg, D2-like receptor antagonist) previously IN-DA (2 mg/kg). Independent groups of rats treated with IN-DA were submitted to prey versus snake paradigm (PSP), ETM and OF. Results: Anti-aversive effects of the IN-DA were reduced by SUL pretreatment in the ES-dPAG test. IN-DA did not affect the escape number in the PSP nor the escape latencies in the ETM as well as motor performance in the OF. Conclusions/interpretation: The IN-DA effects in reducing unconditioned fear responses elicited by ES-dPAG seem to be mediated by D2-like receptors. The lack of effects on panic-related responses in the ETM and PSP may be related to the possibility of avoiding the danger inherent to these models, a defence strategy not available during ES-dPAG. These findings cannot be attributed to motor performance. The decision-making responses to avoid dangerous situations can be orchestrated by supra-mesencephalic structures connected by non-dopaminergic inputs.

Panicolytic‐like effects of environment enrichment on male mice threatened by Bothrops jararaca lancehead pit vipers

“…Researchers have found that predator versus prey confrontations can evoke innate fear‐related reactions in prey animals, making them a useful model for studying defense‐related behaviors (Blanchard et al., 2005; Calvo, Almada, et al., 2019; Calvo, Lobão‐Soares, et al., 2019; Mendes‐Gomes, Motta, et al., 2020; Mendes‐Gomes, Paschoalin‐Maurin, et al., 2020). Using polygonal arenas and complex labyrinths, these studies aim to distinguish between different types of escape behaviors and identify potential treatments for anxiety and panic disorders (de Figueiredo et al., 2022; dos Anjos‐Garcia & Coimbra, 2019, 2020; Guimarães‐Costa et al., 2007; Lobão‐Soares et al., 2008). By embracing naturalistic models, researchers are making strides toward a better understanding of fear and the development of more effective treatments (Twardowschy et al., 2013; Uribe‐Mariño et al., 2012).…”