Chronic methylphenidate administration in mice produces depressive-like behaviors and altered responses to fluoxetine
Article first published online: 13 JUN 2012
Copyright © 2012 Wiley Periodicals, Inc.
Volume 66, Issue 9, pages 844–847, September 2012
How to Cite
Brookshire, B. R. and Jones, S. R. (2012), Chronic methylphenidate administration in mice produces depressive-like behaviors and altered responses to fluoxetine. Synapse, 66: 844–847. doi: 10.1002/syn.21569
- Issue published online: 3 JUL 2012
- Article first published online: 13 JUN 2012
- Accepted manuscript online: 15 MAY 2012 08:10AM EST
- Manuscript Accepted: 7 MAY 2012
- Manuscript Received: 12 MAR 2012
- forced swim test;
- depressive-like behaviour;
- locomotor activity
Methylphenidate (MPH) is a psychostimulant used in the treatment of attention-deficit/hyperactivity disorder in children and adults. Increasing abuse rates of this drug have raised questions regarding the effects of chronic, high-dose MPH administration. Although the effects of chronic MPH exposure have been well-documented in regard to reward-related behaviors in adolescent and adult animals, there are few studies of the effects of MPH on depressive-like behaviors and antidepressant responses, particularly in adult models. We examined the effects of chronic (14 days) high-dose (20 mg/kg i.p.) MPH exposure on locomotor activity and forced swim test behavior in C57Bl/6J mice. We show that MPH treatment ameliorates the locomotor suppression seen in response to fluoxetine. In addition, chronic MPH treatment produces depressive-like effects in the forced swim test, with decreased latency to first immobility and a trend toward increased immobility. These effects are reversed with acute fluoxetine administration, in contrast to saline-treated animals, which show no response to fluoxetine. The induction of depressive-like behaviors after chronic MPH treatment in adult mice is in agreement with previous studies in adolescent rats, and the marked alterations in fluoxetine responses implicate alterations in the serotonin system and possibly the dopamine system produced by MPH. Synapse 66:844–847, 2012. © 2012 Wiley Periodicals, Inc.