Dopamine and norepinephrine receptors participate in methylphenidate enhancement of in vivo hippocampal synaptic plasticity

Abstract

Attention-deficit hyperactive disorder (ADHD) is the most commonly studied and diagnosed psychiatric disorder in children. Methylphenidate (MPH, e.g., Ritalin) has been used to treat ADHD for over 50 years. It is the most commonly prescribed treatment for ADHD, and in the past decade it was the drug most commonly prescribed to teenagers. In addition, MPH has become one of the most widely abused drugs on college campuses. In this study, we examined the effects of MPH on hippocampal synaptic plasticity, which serves as a measurable quantification of memory mechanisms. Field potentials were recorded with permanently implanted electrodes in freely-moving mice to quantify MPH modulation of perforant path synaptic transmission onto granule cells of the dentate gyrus. Our hypothesis was that MPH affects hippocampal synaptic plasticity underlying learning because MPH boosts catecholamine signaling by blocking the dopamine and norepinephrine transporters (DAT and NET respectively). In vitro hippocampal slice experiments indicated MPH enhances perforant path plasticity, and this MPH enhancement arose from action via D1-type dopamine receptors and β-type adrenergic receptors. Similarly, MPH boosted in vivo initiation of long-term potentiation (LTP). While there was an effect via both dopamine and adrenergic receptors in vivo, LTP induction was more dependent on the MPH-induced action via D1-type dopamine receptors. Under biologically reasonable experimental conditions, MPH enhances hippocampal synaptic plasticity via catecholamine receptors.

Methamphetamine‐induced enhancement of hippocampal long‐term potentiation is modulated by NMDA and GABA receptors in the shell–accumbens

“…In the present work, we found systemic METH treatment enhances DG‐LTP in rats. These data are consistent with a recent report showing a similar effect for methylphenidate on DG‐LTP (Jenson et al, ). The DG receives dopaminergic innervation from VTA and contains dopamine D1/D5 receptors (Fremeau et al, ; Gangarossa et al, ; Meador‐Woodruff et al, ).…”

“…The dentate gyrus (DG) is one of hippocampal areas involved in several forms of synaptic plasticity, such as long‐term potentiation (LTP) (Blaise and Hartman, ). Different addictive drugs have been shown to modulate synaptic plasticity in the DG (Creed and Lüscher, ; Hu et al, 2012; Jenson et al, ; Lüscher and Malenka, 2011). Methamphetamine (METH) is one of the most abused psychostimulants.…”

Dopamine Regulates Aversive Contextual Learning and Associated In Vivo Synaptic Plasticity in the Hippocampus

“…Physiological evidence demonstrated that D1 and D5 receptors are important for controlling spike timing dependent plasticity within the hippocampus (Yang and Dani, 2014). Also, there is functional evidence that indicates that drugs of abuse, such as nicotine (Tang and Dani, 2009; Zhang et al, 2010) and methylphenidate (Jenson et al, 2015), recruit dopaminergic neurotransmission to influence synaptic plasticity within the hippocampus. Dopaminergic neurotransmission in the hippocampus during specific time points in the retention interval also seem to be important for successful consolidation of long-term memories (Rossato et al, 2009).…”

Glyphosate Use Predicts Healthcare Utilization for ADHD in the Healthcare Cost and Utilization Project net (HCUPnet): A Two-Way Fixed-Effects Analysis

“…The dopaminergic system was shown to mediate the antinociceptive effects of N 2 O [24], and levels of central neurotransmitters, dopamine (DA), and norepinephrine (NE) were significantly elevated after repeated N 2 O exposure in CD-1 mice [25]. Dysregulation of both catecholamine systems has been implicated in ADHD [26].…”