Serotonergic treatment normalizes midbrain dopaminergic neuron increase after periaqueductal gray stimulation-induced anticipatory fear in a rat mode

Tan, S.Z.K., Temel, Y., Chan, A.Y., Mok, A.T.C., Perucho, J.A.U., Blokland, A., Aquili, L., Lim, W.L. and Lim, L.W. (2019) Serotonergic treatment normalizes midbrain dopaminergic neuron increase after periaqueductal gray stimulation-induced anticipatory fear in a rat mode. bioRxiv .

Abstract

Background: Electrical stimulation of the dorsolateral periaqueductal gray (dlPAG) in rats has been shown to elicit panic-like behaviour and can be a useful tool for modelling anticipatory fear and agoraphobia.

Methods: In this study, we further analysed our previous data on the effects of escitalopram (a selective serotonin reuptake inhibitor, SSRI) and buspirone (a 5-HT1A receptor partial agonist) on dlPAG-induced anticipatory fear behaviour in a rat model using freezing as a measure. We then used tyrosine hydroxylase (TH) immunohistochemistry to probe the effects on dopaminergic neurons.

Results: Although acute treatment of escitalopram, but not buspirone, was effective in reducing anticipatory freezing behaviour, chronic administrations of both drugs were comparably effective. We found that the number of dopaminergic neurons in the ventral tegmental area (VTA) was lowered in both chronic buspirone and escitalopram groups. We showed a strong correlation between the number of dopaminergic neurons and freezing in the VTA. We further showed positive correlations between dopaminergic neurons in the VTA and substantia nigra pars compacta in escitalopram and buspirone groups, respectively.

Limitations: Although our data strongly hint to a role of dopaminergic mechanisms in the dlPAG induced fear response, more in-depth studies with larger sample sizes are needed to understand the neuronal mechanisms underlying the interactions between serotonergic drugs and dopaminergic cell number and fear behavior.

Conclusion: Chronic treatment with an SSRI and a 5-HT1A agonist decrease the number of dopaminergic neurons in the VTA. These effects seem to be associated with reduced dlPAG-induced anticipatory freezing behaviour.

Item Type:	Non-refereed Article
Publisher:	Cold Spring Habor Laboratory
URI:	http://researchrepository.murdoch.edu.au/id/eprint/64215

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