Skip to main content

Prefrontal cortex glutamate afferents are essential for acute and chronic effects of Ritalin


Progressive augmentation of behavioral response following repeated psychostimulant administrations is known as behavioral sensitization, and is an experimental indicator of a drug's liability for abuse (Robinson and Berridge, 1993; Dafny and Yang, 2006). It is known that Ritalin or methylphenidate (MPD), a drug used to treat Attention-Deficit Hyperactivity Disorder (ADHD), induces sensitization in animals following repeated injections [1, 2]. Given that many children suffer ADHD, and are treated with MPD, it is essential to know the neuronal circuitry of MPD action. It was recently reported that bilateral electric (non-specific) lesion of PFC prevented behavioral sensitization after chronic MPD administration (Lee et. al., 2008). Since the PFC sends glutamatergic afferents to both ventral tegmental area (VTA) and nucleus accumbens (NAc), sites that are involved in induction and expression of behavioral sensitization to psychostimulants and as PFC glutamatergic afferents are known to modulate the NAc and VTA dopaminergic neurons [3, 4], the objective of this study was to study the role of glutamate from PFC in behavioral sensitization to MPD.

Materials and methods

Locomotor activity of three groups of rats- control, sham operated and group with specific chemical lesion of glutamate neurons of PFC- was recorded using an open-field assay and analyzed. Daily MPD injections were given to all groups on days 9-14 and the animals were rechallenged on the last day after 4 days of washout.


It was found that the acute and chronic effects of MPD were eliminated in the lesion group.


Therefore, PFC glutamatergic afferents are essential for the MPD-induced hyperactivity and are also involved in its chronic effects such as behavioral sensitization to multiple MPD administrations.


  1. 1.

    Askenasy EP, Taber KH, Yang PB, Dafny N: Methylphenidate (Ritalin): behavioral studies in the rat. Int J Neurosci. 2007, 117: 757-794. 10.1080/00207450600910176.

    CAS  Article  PubMed  Google Scholar 

  2. 2.

    Dafny N, Yang PB: The role of age, genotype, sex, and route of acute and chronic administration of methylphenidate: a review of its locomotor effects. Brain Res Bul. 2006, 68: 393-405. 10.1016/j.brainresbull.2005.10.005.

    CAS  Article  Google Scholar 

  3. 3.

    Kalivas PW, Alesdatter JE: Involvement of NMDA receptor stimulation in the VTA and amygdale in behavioral sensitization to cocaine. J Pharmacol Exp Ther. 1993, 267: 486-495.

    CAS  PubMed  Google Scholar 

  4. 4.

    Kalivas PW: A role of glutamate transmission in addiction to psychostimulants. Addiction Biology. 2000, 5: 325-329. 10.1111/j.1369-1600.2000.tb00199.x.

    CAS  Article  PubMed  Google Scholar 

Download references

Author information



Corresponding author

Correspondence to Sheshali Wanchoo.

Rights and permissions

Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Reprints and Permissions

About this article

Cite this article

Wanchoo, S., Swann, A. & Dafny, N. Prefrontal cortex glutamate afferents are essential for acute and chronic effects of Ritalin. Ann Gen Psychiatry 9, S88 (2010).

Download citation


  • Glutamate
  • Ritalin
  • Ventral Tegmental Area
  • Chronic Effect
  • Behavioral Sensitization