Methylphenidate induces a different response in the dorsal raphe as compared to ventral tegmental area and locus coeruleus: behavioral and concomitant neuronal recordings in adult rats

Yuan, Anthony; Claussen, Catherine M.; Jones, Zachary; Tang, Bin; Dafny, Nachum

doi:10.1007/s00702-023-02665-y

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“…The VTA is composed of dopaminergic, glutamatergic, as well as GABAergic neurons, making it a heterogenous group of neurons. 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].…”

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confidence: 99%

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

Reyes-Vasquez,

Jones,

Tang

et al. 2023

IJMS

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Methylphenidate (MPD), known as Ritalin, is a psychostimulant used to treat children, adults, and the elderly. MPD exerts its effects through increasing concentrations of dopamine (DA), norepinephrine (NE), and serotonin (5-HT) in the synaptic cleft. Concomitant behavioral and neuronal recording from the ventral tegmental area (VTA), locus coeruleus (LC), and from the dorsal raphe (DR) nucleus, which are the sources of DA, NE, and 5-HT to the mesocorticolimbic circuit, were investigated following acute and repetitive (chronic) saline, 0.6, 2.5, or 10.0 mg/kg MPD. Animals received daily saline or MPD administration on experimental days 1 to 6 (ED1–6), followed by a 3-day washout period and MPD rechallenge on ED10. Each chronic MPD dose elicits behavioral sensitization in some animals while inducing behavioral tolerance in others. The uniqueness of this study is in the evaluation of neuronal activity based on the behavioral response to chronic MPD. Neuronal excitation was observed mainly in brain areas of animals exhibiting behavioral sensitization, while neuronal attenuation following chronic MPD was observed in animals expressing behavioral tolerance. Different ratios of excitatory/inhibitory neuronal responses were obtained from the VTA, LC, or DR following chronic MPD. Thus, each brain area responds differently to each MPD dose used, suggesting that DA, NE, and 5-HT in the VTA, LC, and DR exert different effects.

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