TY - JOUR T1 - Chronic treatment with low doses of methamphetamine promotes neuronal differentiation and strengthens long-term potentiation of glutamatergic synapses onto dentate granule neurons JF - eneuro JO - eneuro DO - 10.1523/ENEURO.0141-16.2016 SP - ENEURO.0141-16.2016 AU - Sofia Baptista AU - Joana Lourenço AU - Nuno Milhazes AU - Fernanda Borges AU - Ana Paula Silva AU - Alberto Bacci Y1 - 2016/06/23 UR - http://www.eneuro.org/content/early/2016/06/22/ENEURO.0141-16.2016.abstract N2 - Methamphetamine (METH) is a psychostimulant, affecting hippocampal function with disparate cognitive effects, which depends on the dose and time of administration, ranging from improvement to impairment of memory. Importantly, in the USA, METH is approved for the treatment of Attention-Deficit Hyperactivity Disorder (ADHD). Modifications of long-term plasticity of synapses originating from the entorhinal cortex onto dentate granule cells (DGCs) have been proposed to underlie cognitive alterations similar to those seen in METH users. However, the effects of METH on synaptic plasticity of the dentate gyrus (DG) are unknown. Here, we investigated the impact of chronic administration of METH (2 mg/kg/day) on neurogenesis and synaptic plasticity of immature and mature DGCs of juvenile mice. We used a mouse model of neurogenesis (the G42 line of GAD67-GFP), in which GFP is expressed by differentiating young DGCs. METH treatment enhanced the differentiation of GFP+ cells, as it increased the fraction of GFP+ cells expressing the neuronal marker NeuN, and decreased the amount of immature DGCs co-expressing doublecortin (DCX). Interestingly, METH did not change the magnitude of long-term potentiation (LTP) in more immature neurons, but facilitated LTP induction in more differentiated GFP+ and strengthened plasticity in mature GFP- DGCs. The METH-induced facilitation of LTP in GFP+ neurons was accompanied with spine enlargement. Our results reveal a specific action of chronic use of METH in long-term plasticity of excitatory synapses onto differentiating DGCs and might have important implications towards the understanding of the synaptic basis of METH-induced cognitive alterations.SIGNIFICANCE STATEMENT: METH abuse/misuse can induce memory deficits, but controlled drug prescription is FDA approved for the treatment of Attention-Deficit Hyperactivity Disorder (ADHD). Additionally, DG neurogenesis contributes to the formation and consolidation of new memories. We therefore studied the effects of 7-day exposure to a low dose of METH in DG neurogenesis as well as its impact in synaptic plasticity. We observed that METH accelerated immature neuron differentiation and facilitates LTP in more differentiated immature neurons and mature DGCs. These effects might be the synaptic correlate of some of METH-induced memory alterations. ER -