The key element of dopamine (DA) neurotransmission is undoubtedly DA transporter (DAT), a transmembrane protein responsible for the synaptic reuptake of the mediator. Changes in DAT’s function can be a key mechanism of pathological conditions associated with hyperdopaminer- gia. The first strain of gene-modified rodents with a lack of DAT were created more than 25 years ago. Such animals are characterized by increased levels of striatal DA, resulting in locomotor hyperactivity, increased levels of motor stereotypes, cognitive deficits, and other behavioral abnormalities. The administration of dopaminergic and pharmacological agents affecting other neurotransmitter systems can mitigate those abnormalities. The main purpose of this review is to systematize and analyze (1) known data on the consequences of changes in DAT expression in experimental animals, (2) results of pharmacological studies in these animals, and (3) to estimate the validity of animals lacking DAT as models for discovering new treatments of DA-related disorders.

Dopamine Transporter Deficient Rodents: Perspectives and Limitations for Neuroscience / A. Savchenko, G. Targa, Z. Fesenko, D. Leo, R.R. Gainetdinov, I. Sukhanov. - In: BIOMOLECULES. - ISSN 2218-273X. - 13:5(2023 May 09), pp. 806.1-806.20. [10.3390/biom13050806]

Dopamine Transporter Deficient Rodents: Perspectives and Limitations for Neuroscience

G. Targa
Secondo
;
2023

Abstract

The key element of dopamine (DA) neurotransmission is undoubtedly DA transporter (DAT), a transmembrane protein responsible for the synaptic reuptake of the mediator. Changes in DAT’s function can be a key mechanism of pathological conditions associated with hyperdopaminer- gia. The first strain of gene-modified rodents with a lack of DAT were created more than 25 years ago. Such animals are characterized by increased levels of striatal DA, resulting in locomotor hyperactivity, increased levels of motor stereotypes, cognitive deficits, and other behavioral abnormalities. The administration of dopaminergic and pharmacological agents affecting other neurotransmitter systems can mitigate those abnormalities. The main purpose of this review is to systematize and analyze (1) known data on the consequences of changes in DAT expression in experimental animals, (2) results of pharmacological studies in these animals, and (3) to estimate the validity of animals lacking DAT as models for discovering new treatments of DA-related disorders.
dopamine transporter; hyperdopaminergia; hypodopaminergia; dopamine transporter knockout rodents; locomotor hyperactivity
Settore BIO/14 - Farmacologia
9-mag-2023
https://www.mdpi.com/2218-273X/13/5/806
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/974272
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