TY - JOUR
T1 - The Effects of Norepinephrine Transporter Inactivation on Locomotor Activity in Mice
AU - Mitchell, Heather A.
AU - Ahern, Todd H.
AU - Liles, L. Cameron
AU - Javors, Martin A.
AU - Weinshenker, David
N1 - Funding Information:
This work was supported in part by the Epilepsy Foundation and the National Alliance for Research on Schizophrenia and Depression (to DW).
PY - 2006/11/15
Y1 - 2006/11/15
N2 - Background: Acute administration of different classes of antidepressants can enhance or reduce spontaneous locomotor activity in a novel environment, but the effects of chronic antidepressant treatment on spontaneous locomotor activity in novel and familiar environments are less well characterized. Because norepinephrine is an important regulator of spontaneous locomotor activity, we speculated that norepinephrine transporter blockade contributes to the effects of some antidepressants on spontaneous locomotor activity. Methods: Antidepressant drugs (reboxetine, desipramine, imipramine, venlafaxine, bupropion) were administered acutely (intraperitoneal) or chronically (via osmotic minipump) to control and norepinephrine transporter knockout mice, and spontaneous locomotor activity in novel or familiar environments was recorded. Results: Acute treatment with most norepinephrine transporter-blocking antidepressants decreased spontaneous locomotor activity in a novel environment, whereas chronic treatment decreased spontaneous locomotor activity in both novel and familiar environments. The exception was bupropion, a dual norepinephrine transporter/dopamine transporter blocker, which tended to increase spontaneous locomotor activity. Coadministration of reboxetine and the dopamine transporter blocker GBR 12909 also increased spontaneous locomotor activity. Norepinephrine transporter knockout mice had low basal spontaneous locomotor activity, which was increased by bupropion, whereas reboxetine had no effect in norepinephrine transporter knockout mice. Conclusions: Acute or chronic inactivation of the norepinephrine transporter decreases spontaneous locomotor activity in novel and familiar environments unless coupled with dopamine transporter blockade.
AB - Background: Acute administration of different classes of antidepressants can enhance or reduce spontaneous locomotor activity in a novel environment, but the effects of chronic antidepressant treatment on spontaneous locomotor activity in novel and familiar environments are less well characterized. Because norepinephrine is an important regulator of spontaneous locomotor activity, we speculated that norepinephrine transporter blockade contributes to the effects of some antidepressants on spontaneous locomotor activity. Methods: Antidepressant drugs (reboxetine, desipramine, imipramine, venlafaxine, bupropion) were administered acutely (intraperitoneal) or chronically (via osmotic minipump) to control and norepinephrine transporter knockout mice, and spontaneous locomotor activity in novel or familiar environments was recorded. Results: Acute treatment with most norepinephrine transporter-blocking antidepressants decreased spontaneous locomotor activity in a novel environment, whereas chronic treatment decreased spontaneous locomotor activity in both novel and familiar environments. The exception was bupropion, a dual norepinephrine transporter/dopamine transporter blocker, which tended to increase spontaneous locomotor activity. Coadministration of reboxetine and the dopamine transporter blocker GBR 12909 also increased spontaneous locomotor activity. Norepinephrine transporter knockout mice had low basal spontaneous locomotor activity, which was increased by bupropion, whereas reboxetine had no effect in norepinephrine transporter knockout mice. Conclusions: Acute or chronic inactivation of the norepinephrine transporter decreases spontaneous locomotor activity in novel and familiar environments unless coupled with dopamine transporter blockade.
KW - Norepinephrine transporter
KW - antidepressant
KW - chronic
KW - knockout
KW - locomotor activity
KW - mice
UR - http://www.scopus.com/inward/record.url?scp=33750484686&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33750484686&partnerID=8YFLogxK
U2 - 10.1016/j.biopsych.2006.03.057
DO - 10.1016/j.biopsych.2006.03.057
M3 - Article
C2 - 16893531
AN - SCOPUS:33750484686
SN - 0006-3223
VL - 60
SP - 1046
EP - 1052
JO - Biological Psychiatry
JF - Biological Psychiatry
IS - 10
ER -