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

J Psychopharmacol. 2022 Nov;36(11):1257-1272. doi: 10.1177/02698811221128018. Epub 2022 Oct 14.

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.

Keywords: Dopamine; nasal drug application; unconditioned fear.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Crotalinae*
  • Dopamine / pharmacology
  • Electric Stimulation
  • Escape Reaction
  • Fear
  • Periaqueductal Gray*
  • Rats
  • Rats, Wistar

Substances

  • Dopamine