Behavioral characterization of DAT-KO rats and evidence of asocial-like phenotypes in DAT-HET rats: The potential involvement of norepinephrine system

Annalisa Adinolfi, Silvia Zelli, Damiana Leo, Cristiana Carbone, Liudmila Mus, Placido Illiano, Enrico Alleva, Raul R. Gainetdinov, Walter Adriani

Research output

1 Citation (Scopus)

Abstract

Dopamine (DA) is a key neurotransmitter of the central nervous system, whose availability is regulated by the dopamine transporter (DAT). Deletion of DAT gene leading to hyperdopaminergia was previously performed on mouse models. This enabled recapitulation of the core symptoms of Attention-Deficit / Hyper-activity Disorder (ADHD), which include hyperactivity, inattention and cognitive impairment. We used recently developed DAT knockout (DAT-KO) rats to carry out further behavioral profiling on this novel model of hyperdopaminergia. DAT-KO rats display elevated locomotor activity and restless environmental exploration, associated with a transient anxiety profile. Furthermore, these rats show pronounced stereotypy and compulsive-like behavior at the Marble-Burying test. Homozygous DAT-KO rats mantain intact social interaction when tested in a social-preference task, while heterozygous (HET) rats show high inactivity associated with close proximity to the social stimulus. Ex-vivo evaluation of brain catecholamines highlighted increased levels of norepinephrine in the hippocampus and hypothalamus exclusively of heterozygous rats. Taken together, our data present evidence of unexpected asocial tendencies in heterozygous (DAT-HET) rats associated with neurochemical alterations in norepinephrine neurotransmission. We shed light on the behavioral and neurochemical consequences of altered DAT function in a higher, more complex model of hyperdopaminergia. Unraveling the role of DA neurotransmission in DAT-KO rats has very important implications in the understanding of many psychiatric illnesses, including ADHD, where alterations in DA system have been demonstrated.

Original languageEnglish
Pages (from-to)516-527
JournalBehavioural Brain Research
Volume359
Early online date22 Feb 2018
DOIs
Publication statusPublished - 1 Feb 2019

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Dopamine Plasma Membrane Transport Proteins
Norepinephrine
Phenotype
Dopamine
Synaptic Transmission
Compulsive Behavior
Calcium Carbonate
Locomotion
Interpersonal Relations
Hypothalamus
Catecholamines
Neurotransmitter Agents
Psychiatry
Hippocampus
Anxiety
Central Nervous System
Brain

Scopus subject areas

  • Behavioral Neuroscience

Cite this

Adinolfi, Annalisa ; Zelli, Silvia ; Leo, Damiana ; Carbone, Cristiana ; Mus, Liudmila ; Illiano, Placido ; Alleva, Enrico ; Gainetdinov, Raul R. ; Adriani, Walter. / Behavioral characterization of DAT-KO rats and evidence of asocial-like phenotypes in DAT-HET rats : The potential involvement of norepinephrine system. In: Behavioural Brain Research. 2019 ; Vol. 359. pp. 516-527.
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Behavioral characterization of DAT-KO rats and evidence of asocial-like phenotypes in DAT-HET rats : The potential involvement of norepinephrine system. / Adinolfi, Annalisa; Zelli, Silvia; Leo, Damiana; Carbone, Cristiana; Mus, Liudmila; Illiano, Placido; Alleva, Enrico; Gainetdinov, Raul R.; Adriani, Walter.

In: Behavioural Brain Research, Vol. 359, 01.02.2019, p. 516-527.

Research output

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T2 - The potential involvement of norepinephrine system

AU - Adinolfi, Annalisa

AU - Zelli, Silvia

AU - Leo, Damiana

AU - Carbone, Cristiana

AU - Mus, Liudmila

AU - Illiano, Placido

AU - Alleva, Enrico

AU - Gainetdinov, Raul R.

AU - Adriani, Walter

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AB - Dopamine (DA) is a key neurotransmitter of the central nervous system, whose availability is regulated by the dopamine transporter (DAT). Deletion of DAT gene leading to hyperdopaminergia was previously performed on mouse models. This enabled recapitulation of the core symptoms of Attention-Deficit / Hyper-activity Disorder (ADHD), which include hyperactivity, inattention and cognitive impairment. We used recently developed DAT knockout (DAT-KO) rats to carry out further behavioral profiling on this novel model of hyperdopaminergia. DAT-KO rats display elevated locomotor activity and restless environmental exploration, associated with a transient anxiety profile. Furthermore, these rats show pronounced stereotypy and compulsive-like behavior at the Marble-Burying test. Homozygous DAT-KO rats mantain intact social interaction when tested in a social-preference task, while heterozygous (HET) rats show high inactivity associated with close proximity to the social stimulus. Ex-vivo evaluation of brain catecholamines highlighted increased levels of norepinephrine in the hippocampus and hypothalamus exclusively of heterozygous rats. Taken together, our data present evidence of unexpected asocial tendencies in heterozygous (DAT-HET) rats associated with neurochemical alterations in norepinephrine neurotransmission. We shed light on the behavioral and neurochemical consequences of altered DAT function in a higher, more complex model of hyperdopaminergia. Unraveling the role of DA neurotransmission in DAT-KO rats has very important implications in the understanding of many psychiatric illnesses, including ADHD, where alterations in DA system have been demonstrated.

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