Methylphenidate has long-lasting metaplastic effects in the prefrontal cortex of adolescent rats.

Abstract:

:Methylphenidate (MPH) is widely used as a "nootropic" agent and in the treatment of disorders of attention, and has been shown to modulate synaptic plasticity in vitro. Here we present in vivo evidence that this MPH-induced metaplasticity can last long after the end of treatment. MPH (0, 0.2, 1 and 5mg/kg) was administered daily to male rats from postnatal day 42 for 15 days. The animals were tested daily in a radial maze. Long-term potentiation (LTP), a marker of neural plasticity, was induced in vivo in the prefrontal cortex after 2-3h, 15-18 days or 5 months without treatment. The behavioral performance of the 1mg/kg group improved, while that of animals that had received 5mg/kg deteriorated. In the 1 and 5mg/kg groups LTP induced 2-3h after the last MPH treatment was twice as large as in the controls. Further, 15-18 days after the last MPH administration, in groups receiving 1 and 5mg/kg, LTP was about fourfold higher than in controls. However, 5 months later, LTP in the 1mg/kg group was similar to controls and in the 5mg/kg group LTP could not be induced at all. No significant changes of LTP were seen in the low-dose group of animals (0.2mg/kg). Thus, firstly, doses of MPH that improve learning coincide approximately with those that augment LTP. Secondly, MPH-induced increases in LTP can last for several weeks, but these may disappear over longer periods or deteriorate at high doses.

journal_name

Behav Brain Res

authors

Burgos H,Cofré C,Hernández A,Sáez-Briones P,Agurto R,Castillo A,Morales B,Zeise ML

doi

10.1016/j.bbr.2015.05.009

subject

Has Abstract

pub_date

2015-09-15 00:00:00

pages

112-117

eissn

0166-4328

issn

1872-7549

pii

S0166-4328(15)00338-1

journal_volume

291

pub_type

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