Acute Depletion of D2 Receptors from the Rat Substantia Nigra Alters Dopamine Kinetics in the Dorsal Striatum and Drug Responsivity

Budygin, Evgeny A. and Oleson, Erik B. and Lee, Yun Beom and Blume, Lawrence C. and Bruno, Michael J. and Howlett, Allyn C. and Thompson, Alexis C. and Bass, Caroline E. (2017) Acute Depletion of D2 Receptors from the Rat Substantia Nigra Alters Dopamine Kinetics in the Dorsal Striatum and Drug Responsivity. Frontiers in Behavioral Neuroscience, 10. ISSN 1662-5153

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Abstract

Recent studies have used conditional knockout mice to selectively delete the D2 autoreceptor; however, these approaches result in global deletion of D2 autoreceptors early in development. The present study takes a different approach using RNA interference (RNAi) to knockdown the expression of the D2 receptors (D2R) in the substantia nigra (SN), including dopaminergic neurons, which project primarily to the dorsal striatum (dStr) in adult rats. This approach restricts the knockdown primarily to nigrostriatal pathways, leaving mesolimbic D2 autoreceptors intact. Analyses of dopamine (DA) kinetics in the dStr reveal a decrease in DA transporter (DAT) function in the knockdown rats, an effect not observed in D2 autoreceptor knockout mouse models. SN D2 knockdown rats exhibit a behavioral phenotype characterized by persistent enhancement of locomotor activity in a familiar open field, reduced locomotor responsiveness to high doses of cocaine and the ability to overcome haloperidol-induced immobility on the bar test. Together these results demonstrate that presynaptic D2R can be depleted from specific neuronal populations and implicates nigrostriatal D2R in different behavioral responses to psychotropic drugs.

Item Type: Article
Subjects: Afro Asian Archive > Biological Science
Depositing User: Unnamed user with email support@afroasianarchive.com
Date Deposited: 21 Feb 2023 09:59
Last Modified: 06 Jul 2024 07:56
URI: http://info.stmdigitallibrary.com/id/eprint/228

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