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Dopamine D2 receptors in the expression and extinction of contextual and cued conditioned fear in rats

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Abstract

Dopamine seems to mediate fear conditioning through its action on D2 receptors in the mesolimbic pathway. Systemic and local injections of dopaminergic agents showed that D2 receptors are preferentially involved in the expression, rather than in the acquisition, of conditioned fear. To further examine this issue, we evaluated the effects of systemic administration of the dopamine D2-like receptor antagonists sulpiride and haloperidol on the expression and extinction of contextual and cued conditioned fear in rats. Rats were trained to a context-CS or a light-CS using footshocks as unconditioned stimuli. After 24 h, rats received injections of sulpiride or haloperidol and were exposed to the context-CS or light-CS for evaluation of freezing expression (test session). After another 24 h, rats were re-exposed to the context-CS or light-CS, to evaluate the extinction recall (retest session). Motor performance was assessed with the open-field and catalepsy tests. Sulpiride, but not haloperidol, significantly reduced the expression of contextual and cued conditioned fear without affecting extinction recall. In contrast, haloperidol, but not sulpiride, had cataleptic and motor-impairing effects. The results reinforce the importance of D2 receptors in fear conditioning and suggest that dopaminergic mechanisms mediated by D2 receptors are mainly involved in the expression rather than in the extinction of conditioned freezing.

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Data availability statement

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

This study was supported by the São Paulo Research Foundation (FAPESP—Proc. No. 2016/04620-1), the Brazilian National Council for Scientific and Technological Development (CNPq—Proc. No. 401032/2016-7), and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES—Finance Code 001).

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  1. Department of Psychology, Federal University of São Carlos (UFSCar), São Carlos, SP, Brazil

    Vivian M. de Vita, Heloisa R. Zapparoli, Adriano E. Reimer & Amanda R. de Oliveira

  2. Institute of Neuroscience and Behavior (INeC), Ribeirão Preto, SP, Brazil

    Adriano E. Reimer, Marcus L. Brandão & Amanda R. de Oliveira

  3. Department of Psychiatry, University of Minnesota, Minneapolis, MN, USA

    Adriano E. Reimer

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  1. Vivian M. de Vita
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de Vita, V.M., Zapparoli, H.R., Reimer, A.E. et al. Dopamine D2 receptors in the expression and extinction of contextual and cued conditioned fear in rats. Exp Brain Res 239, 1963–1974 (2021). https://doi.org/10.1007/s00221-021-06116-6

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