Development of hyperactivity and anxiety responses in dopamine transporter-deficient mice

Carpenter, Alex C; Saborido, Tommy; Stanwood, Gregg D.

doi:10.1016/j.ntt.2013.03.053

Cited by 6 publications

(6 citation statements)

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“…More importantly, these effects were region specific as DAT manipulation in the CPu had no effect. Our findings are perfectly in line with previously published studies using DAT deficient mice in which anxiety-like behavior seemed to be reduced, compared to WT controls, in the EPM and LDB assays [68]. Also, and compared to WT, DAT KO mice spent more time in the OA, suggesting that they were less anxious in the EPM test, with no indication of hyperactivity, as both genotypes showed the same number of total entries [69].…”

Section: Discussionsupporting

confidence: 92%

Dopamine transporter (DAT) knockdown in the nucleus accumbens improves anxiety- and depression-related behaviors in adult mice

Bahí

Dreyer

2019

Behavioural Brain Research

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Many epidemiological and clinical studies have demonstrated a strong comorbidity between anxiety and depression, and a number of experimental studies indicates that the dopamine transporter (DAT) is involved in the pathophysiology of anxiety and depression. However, studies using laboratory animals have yielded inconclusive results. The aim of the present study was to examine the effects of DAT manipulation on anxiety-and depression-like behaviors in mice. For this purpose, animals were stereotaxically injected with DAT siRNAexpressing lentiviral vectors (siDAT) in the caudate putamen (CPu) or in the nucleus accumbens (Nacc) and the behavioral outcomes were assessed using the open-field (OF), elevated-plus maze (EPM), light-dark box (LDB), sucrose preference (SPT), novelty suppressed feeding (NSF), and forced-swim (FST) tests. The results showed that in the Nacc, but not in the CPu, siDAT increased the time spent at the center of the arena and decreased the number of fecal boli in the OF test. In the EPM and LDB tests, Nacc siDAT injection increased the entries and time spent on open arms, and increased the time spent in the light side of the box, respectively, suggesting an anxiolytic-like activity. In addition, siDAT, in the Nacc, induced significant antidepressant-like effects, evidenced by increased sucrose preference, shorter latency to feed in the NSF test, and decreased immobility time in the FST. Most importantly, Pearson's test clearly showed significant correlations between DAT mRNA in the Nacc with anxiety and depression parameters. Overall, these results suggest that low DAT levels, in the Nacc, might act as protective factors against anxiety and depression. Therefore, targeting DAT activity might be a very attractive approach to tackle affective disorders.

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Section: Discussionsupporting

confidence: 92%

Dopamine transporter (DAT) knockdown in the nucleus accumbens improves anxiety- and depression-related behaviors in adult mice

Bahí

Dreyer

2019

Behavioural Brain Research

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“…With regard to additional behaviors, mice developmentally exposed to deltamethrin show deficits in Y‐maze performance, indicative of working memory and attention deficits. However, no change in performance was observed in DAT knockout mice (54).…”

Section: Discussionmentioning

confidence: 91%

Developmental pesticide exposure reproduces features of attention deficit hyperactivity disorder

et al. 2015

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Attention-deficit hyperactivity disorder (ADHD) is estimated to affect 8-12% of school-age children worldwide. ADHD is a complex disorder with significant genetic contributions. However, no single gene has been linked to a significant percentage of cases, suggesting that environmental factors may contribute to ADHD. Here, we used behavioral, molecular, and neurochemical techniques to characterize the effects of developmental exposure to the pyrethroid pesticide deltamethrin. We also used epidemiologic methods to determine whether there is an association between pyrethroid exposure and diagnosis of ADHD. Mice exposed to the pyrethroid pesticide deltamethrin during development exhibit several features reminiscent of ADHD, including elevated dopamine transporter (DAT) levels, hyperactivity, working memory and attention deficits, and impulsive-like behavior. Increased DAT and D1 dopamine receptor levels appear to be responsible for the behavioral deficits. Epidemiologic data reveal that children aged 6-15 with detectable levels of pyrethroid metabolites in their urine were more than twice as likely to be diagnosed with ADHD. Our epidemiologic finding, combined with the recapitulation of ADHD behavior in pesticide-treated mice, provides a mechanistic basis to suggest that developmental pyrethroid exposure is a risk factor for ADHD.

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“…Studies of DAT knockout mice consistently show that decreased DAT levels correspond to increased dopamine turnover and increased synaptic dopamine levels [72]. DAT knockout mice also appear less anxious in the elevated plus maze and other anxiety-relevant paradigms [73]. Hence, it is plausible that upregulation of the DAT leads to the increased clearance of dopamine from the synaptic space, lowered dopamine concentration and lowered dopamine turnover, possibly contributing to reduced motivational drive for, and pleasure from, social interactions.…”

Section: Discussionmentioning

confidence: 99%

Expression and co-expression of serotonin and dopamine transporters in social anxiety disorder: a multitracer positron emission tomography study

et al. 2019

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Serotonin and dopamine are putatively involved in the etiology and treatment of anxiety disorders, but positron emission tomography (PET) studies probing the two neurotransmitters in the same individuals are lacking. The aim of this multitracer PET study was to evaluate the regional expression and co-expression of the transporter proteins for serotonin (SERT) and dopamine (DAT) in patients with social anxiety disorder (SAD). Voxel-wise binding potentials (BP ND ) for SERT and DAT were determined in 27 patients with SAD and 43 age-and sex-matched healthy controls, using the radioligandsResults showed that, within transmitter systems, SAD patients exhibited higher SERT binding in the nucleus accumbens while DAT availability in the amygdala, hippocampus, and putamen correlated positively with symptom severity. At a more lenient statistical threshold, SERT and DAT BP ND were also higher in other striatal and limbic regions in patients, and correlated with symptom severity, whereas no brain region showed higher binding in healthy controls. Moreover, SERT/DAT co-expression was significantly higher in SAD patients in the amygdala, nucleus accumbens, caudate, putamen, and posterior ventral thalamus, while lower co-expression was noted in the dorsomedial thalamus. Follow-up logistic regression analysis confirmed that SAD diagnosis was significantly predicted by the statistical interaction between SERT and DAT availability, in the amygdala, putamen, and dorsomedial thalamus. Thus, SAD was associated with mainly increased expression and co-expression of the transporters for serotonin and dopamine in fear and reward-related brain regions. Resultant monoamine dysregulation may underlie SAD symptomatology and constitute a target for treatment.

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Development of hyperactivity and anxiety responses in dopamine transporter-deficient mice

Cited by 6 publications

References 0 publications

Dopamine transporter (DAT) knockdown in the nucleus accumbens improves anxiety- and depression-related behaviors in adult mice

Dopamine transporter (DAT) knockdown in the nucleus accumbens improves anxiety- and depression-related behaviors in adult mice

Developmental pesticide exposure reproduces features of attention deficit hyperactivity disorder

Expression and co-expression of serotonin and dopamine transporters in social anxiety disorder: a multitracer positron emission tomography study

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