The role of prefrontal cortex dopamine D2 and D3 receptors in the mechanism of action of venlafaxine and deep brain stimulation in animal models of treatment-responsive and treatment-resistant depression

Journal of Psychopharmacology
Mariusz PappPaul Willner

Abstract

The Wistar-Kyoto rat has been validated as an animal model of treatment-resistant depression. Here we investigated a role of dopamine D2 and D3 receptors in the ventro-medial prefrontal cortex in the mechanism of action of deep brain stimulation in Wistar-Kyoto rats and venlafaxine in Wistar rats. Wistar or Wistar-Kyoto rats were exposed chronically to chronic mild stress. Wistar rats were treated chronically with venlafaxine (10 mg/kg) beginning after two weeks of chronic mild stress; Wistar-Kyoto rats received two sessions of deep brain stimulation before behavioural tests. L-742,626 (1 µg), a D2 receptor agonist, or 7-OH DPAT (3 µg), a D3 receptor antagonist, were infused into the ventro-medial prefrontal cortex immediately following the exposure trial in the Novel Object Recognition Test, and discrimination between novel and familiar object was tested one hour later. Chronic mild stress decreased sucrose intake and impaired memory consolidation; these effects were reversed by venlafaxine in Wistar rats and deep brain stimulation in Wistar-Kyoto rats. In control animals, L-742,626 and 7-OH DPAT also impaired memory consolidation. In Wistar rats, venlafaxine reversed the effect of L-742,626 in controls, but not in the chronic...Continue Reading

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Citations

Jun 10, 2021·Neuromodulation : Journal of the International Neuromodulation Society·Jason YuenYoonbae Oh
Jun 16, 2021·British Journal of Pharmacology·Mariusz PappPaul Willner

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