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Chronic methylphenidate administration in mice produces depressive‐like behaviors and altered responses to fluoxetine
Author(s) -
Brookshire Bethany R.,
Jones Sara R.
Publication year - 2012
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.21569
Subject(s) - methylphenidate , fluoxetine , psychology , pharmacology , psychiatry , neuroscience , medicine , serotonin , attention deficit hyperactivity disorder , receptor
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.