+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Animal models of depression in dopamine, serotonin, and norepinephrine transporter knockout mice: prominent effects of dopamine transporter deletions



Animal models of depression in dopamine, serotonin, and norepinephrine transporter knockout mice: prominent effects of dopamine transporter deletions



Behavioural Pharmacology 19(5-6): 566-574



Antidepressant drugs produce therapeutic actions and many of their side effects via blockade of the plasma membrane transporters for serotonin (SERT/SLC6A2), norepinephrine (NET/SLC6A1), and dopamine (DAT/SLC6A3). Many antidepressants block several of these transporters; some are more selective. Mouse gene knockouts of these transporters provide interesting models for possible effects of chronic antidepressant treatments. To examine the role of monoamine transporters in models of depression DAT, NET, and SERT knockout (KO) mice and wild-type littermates were studied in the forced swim test (FST), the tail suspension test, and for sucrose consumption. To dissociate general activity from potential antidepressant effects three types of behavior were assessed in the FST: immobility, climbing, and swimming. In confirmation of earlier reports, both DAT KO and NET KO mice exhibited less immobility than wild-type littermates whereas SERT KO mice did not. Effects of DAT deletion were not simply because of hyperactivity, as decreased immobility was observed in DAT+/- mice that were not hyperactive as well as in DAT-/- mice that displayed profound hyperactivity. Climbing was increased, whereas swimming was almost eliminated in DAT-/- mice, and a modest but similar effect was seen in NET KO mice, which showed a modest decrease in locomotor activity. Combined increases in climbing and decreases in immobility are characteristic of FST results in antidepressant animal models, whereas selective effects on swimming are associated with the effects of stimulant drugs. Therefore, an effect on climbing is thought to more specifically reflect antidepressant effects, as has been observed in several other proposed animal models of reduced depressive phenotypes. A similar profile was observed in the tail suspension test, where DAT, NET, and SERT knockouts were all found to reduce immobility, but much greater effects were observed in DAT KO mice. However, to further determine whether these effects of DAT KO in animal models of depression may be because of the confounding effects of hyperactivity, mice were also assessed in a sucrose consumption test. Sucrose consumption was increased in DAT KO mice consistent with reduced anhedonia, and inconsistent with competitive hyperactivity; no increases were observed in SERT KO or NET KO mice. In summary, the effects of DAT KO in animal models of depression are larger than those produced by NET or SERT KO, and unlikely to be simply the result of the confounding effects of locomotor hyperactivity; thus, these data support reevaluation of the role that DAT expression could play in depression and the potential antidepressant effects of DAT blockade.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 051551507

Download citation: RISBibTeXText

PMID: 18690111

DOI: 10.1097/fbp.0b013e32830cd80f


Related references

Cocaine-conditioned locomotion in dopamine transporter, norepinephrine transporter and 5-HT transporter knockout mice. Neuroscience 162(4): 870-880, 2009

Effects of cocaine in combined dopamine transporter /serotonin transporter and DAT/serotonin 1B receptor knockout mice. Society for Neuroscience Abstracts 27(1): 1180, 2001

Norepinephrine transporter blockade can normalize the prepulse inhibition deficits found in dopamine transporter knockout mice. Neuropsychopharmacology 31(10): 2132-2139, 2006

Serotonin/dopamine interactions in a hyperactive mouse: reduced serotonin receptor 1B activity reverses effects of dopamine transporter knockout. Plos One 9(12): E115009, 2016

Psychostimulant reward models Conditioned place preference can be established in dopamine-and in serotonin-transporter knockout mice. Society for Neuroscience Abstracts 24(1-2): 996, 1998

Cocaine reward models: Conditioned place preference can be established in dopamine- and in serotonin-transporter knockout mice. Proceedings of the National Academy of Sciences of the United States of America 95(13): 7699-7704, 1998

Aging effects on locomotor activity in dopamine transporter and vesicular monoamine transporter knockout mice. Society for Neuroscience Abstracts 26(1-2): Abstract No -344 5, 2000

Effects of paroxetine on serotonin efflux in dopamine transporter knockout mice An in vivo microdialysis study. Society for Neuroscience Abstracts 25(1-2): 162, 1999

Dopamine, norepinephrine and serotonin transporter gene deletions differentially alter cocaine-induced taste aversion. Pharmacology, Biochemistry, and Behavior 94(4): 580-587, 2010

Dopamine dynamics and psychostimulant effects in dopamine transporter knockout mice. Society for Neuroscience Abstracts 22(1-3): 1575, 1996

Effects of cocaine and amphetamine on dopamine clearance in the nucleus accumbens of dopamine transporter knockout mice. Society for Neuroscience Abstract Viewer & Itinerary Planner : Abstract No 536 7, 2002

Rewarding properties of cocaine in dopamine/norepinephrine transporter knockout mice. FASEB Journal 17(4-5): Abstract No 140 8, 2003

Methamphetamine sensitization in dopamine and/or serotonin transporter knockout mice. Society for Neuroscience Abstract Viewer & Itinerary Planner : Abstract No 424 11, 2003

Dopamine uptake in serotonin transporter knockout mice by chronoamperometry. Society for Neuroscience Abstracts 27(2): 1870, 2001

Enhanced cocaine conditioned place preference in combined norepinephrine transporter /serotonin transporter knockout mice. Society for Neuroscience Abstracts 27(1): 1181, 2001