The Ventral Tegmental Area (VTA), the Nucleus Accumbens (NAc), the Caudate Nucleus (CN) and the Prefrontal Cortex (PFC) role in the Response to Acute and Chronic Methylphenidate

Abstract

Methylphenidate (MPD) is psychostimulant, similar to cocaine and amphetamine, that is commonly used to treat attention deficit hyperactivity disorder and is increasingly being abused by healthy subjects for its psychoactive effects such as memory retention cognitive enhancement for young, adult and the elderly and recreation. MPD’s action on the brain reward/motive circuit is still under investigation, however it is known that in animals chronic use of MPD leads to behavioral sensitization, an experimental indicator associated with dependence. To investigate this neural circuit’s role in response to acute and chronic MPD, three different lesions (non-specific, dopaminergic specific, and glutaminergic specific lesions) have been conducted at the nucleus accumbens (NAc), the ventral tegmental area (VTA), the caudate nucleus (CN), and the prefrontal cortex (PFC), to assess the structure, dopaminergic signaling, and glutaminergic signaling roles in response to MPD. The three types of lesions show that each one of the above four brain areas participate differently in the acute and chronic effect of MPD and have helped determine which type of signaling is critical for the acute and/or chronic behavioral adaptions to MPD.

Dopamine, Norepinephrine and Serotonin Participate Differently in Methylphenidate Action in Concomitant Behavioral and Ventral Tegmental Area, Locus Coeruleus and Dorsal Raphe Neuronal Study in Young Rats

“…The medial VTA participates in an inhibitory pathway, while the lateral VTA participates predominantly in the dopaminergic reward pathway [32][33][34]. DA signaling participates in the regulation of attention, cognition, and motor activity [31,35]. The locus coeruleus (LC) are a group of neurons located deep within the brainstem and are the origin of synthesis of NE.…”

“…The locus coeruleus (LC) are a group of neurons located deep within the brainstem and are the origin of synthesis of NE. This region contains many projections that provide far-reaching noradrenergic transmissions throughout the brain [35][36][37]. Noradrenergic signaling within the cortical and subcortical structures regulate attention, memory, and sensation, and the LC is directly involved in the alteration of gene expression that determines executive function, behavior, and arousal [38][39][40][41][42].…”