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

Abstract

Background 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.