Characterisation of methylphenidate-induced excitation in midbrain dopamine neurons, an electrophysiological study in the rat brain

Miceli, Mathieu Di; Omoloye, Adesina; Gronier, Benjamin

doi:10.1016/j.pnpbp.2021.110406

Cited by 4 publications

(2 citation statements)

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“…Several studies investigating the property of MPD on a single CNS structure of acute and chronic MPD on DR [ 27 ], on LC [ 28 ], on VTA [ 14 , 29 ], on NAc [ 14 ], on CN, and on the PFC [ 20 ] reported that MPD exerts similar effects on each of the above six brain areas. Based on our preliminary study using simultaneous neuronal recordings from the above six brain areas, we hypothesize that each of the six brain areas plays a different role in MPD action.…”

Section: Introductionmentioning

confidence: 99%

Differential Roles of Key Brain Regions: Ventral Tegmental Area, Locus Coeruleus, Dorsal Raphe, Nucleus Accumbens, Caudate Nucleus, and Prefrontal Cortex in Regulating Response to Methylphenidate: Insights from Neuronal and Behavioral Studies in Freely Behaving Rats

Dafny,

Claussen,

Frazier

et al. 2024

IJMS

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A total of 3102 neurons were recorded before and following acute and chronic methylphenidate (MPD) administration. Acute MPD exposure elicits mainly increases in neuronal and behavioral activity in dose–response characteristics. The response to chronic MPD exposure, as compared to acute 0.6, 2.5, or 10.0 mg/kg MPD administration, elicits electrophysiological and behavioral sensitization in some animals and electrophysiological and behavioral tolerance in others when the neuronal recording evaluations were performed based on the animals’ behavioral responses, or amount of locomotor activity, to chronic MPD exposure. The majority of neurons recorded from those expressing behavioral sensitization responded to chronic MPD with further increases in firing rate as compared to the initial MPD responses. The majority of neurons recorded from animals expressing behavioral tolerance responded to chronic MPD with decreases in their firing rate as compared to the initial MPD exposures. Each of the six brain areas studied—the ventral tegmental area, locus coeruleus, dorsal raphe, nucleus accumbens, prefrontal cortex, and caudate nucleus (VTA, LC, DR, NAc, PFC, and CN)—responds significantly (p < 0.001) differently to MPD, suggesting that each one of the above brain areas exhibits different roles in the response to MPD. Moreover, this study demonstrates that it is essential to evaluate neuronal activity responses to psychostimulants based on the animals’ behavioral responses to acute and chronic effects of the drug from several brain areas simultaneously to obtain accurate information on each area’s role in response to the drug.

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Section: Introductionmentioning

confidence: 99%

Differential Roles of Key Brain Regions: Ventral Tegmental Area, Locus Coeruleus, Dorsal Raphe, Nucleus Accumbens, Caudate Nucleus, and Prefrontal Cortex in Regulating Response to Methylphenidate: Insights from Neuronal and Behavioral Studies in Freely Behaving Rats

Dafny,

Claussen,

Frazier

et al. 2024

IJMS

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“…Its use started in 1955 as a medication for the elderly to treat locomotor fatigue activities, aiming to prevent falling, sleep disorders, and memory recognition deficits, and is now a widely used drug by all ages. Knowledge about this drug is still quite vague as it remains unclear how it specifically affects neuronal and behavioral activities [1][2][3][4][5][6] MPD is a central nervous system (CNS) stimulant known for its effectiveness in treating behavioral disorders, such as attention deficit hyperactivity disorder (ADHD), and improving cognitive and social functions. More recently, its unregulated use by ordinary young and adults for cognitive enhancement, concentration improvement, and increased productivity and academic performance has become more popular, being coined as a "study drug" or a "smart drug' [7][8][9][10], as well as its abuse for recreational purposes [11,12].…”

Section: Introductionmentioning

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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The potential role of stimulants in treating eating disorders

Keshen

Bartel

Frank

et al. 2021

Intl J Eating Disorders

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Background Many individuals with eating disorders remain symptomatic after a course of psychotherapy and pharmacotherapy; therefore, the development of innovative treatments is essential. Method To learn more about the current evidence for treating eating disorders with stimulants, we searched for original articles and reviews published up to April 29, 2021 in PubMed and MEDLINE using the following search terms: eating disorders, anorexia, bulimia, binge eating, stimulants, amphetamine, lisdexamfetamine, methylphenidate, and phentermine. Results We propose that stimulant medications represent a novel avenue for future research based on the following: (a) the relationship between eating disorders and attention deficit/hyperactivity disorder (ADHD); (b) a neurobiological rationale; and (c) the current (but limited) evidence for stimulants as treatments for some eating disorders. Despite the possible benefits of such medications, there are also risks to consider such as medication misuse, adverse cardiovascular events, and reduction of appetite and pathological weight loss. With those risks in mind, we propose several directions for future research including: (a) randomized controlled trials to study stimulant treatment in those with bulimia nervosa (with guidance on strategies to mitigate risk); (b) examining stimulant treatment in conjunction with psychotherapy; (c) investigating the impact of stimulants on “loss of control” eating in youth with ADHD; and (d) exploring relevant neurobiological mechanisms. We also propose specific directions for exploring mediators and moderators in future clinical trials. Discussion Although this line of investigation may be viewed as controversial by some in the field, we believe that the topic warrants careful consideration for future research.

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Characterisation of methylphenidate-induced excitation in midbrain dopamine neurons, an electrophysiological study in the rat brain

Cited by 4 publications

References 98 publications

Differential Roles of Key Brain Regions: Ventral Tegmental Area, Locus Coeruleus, Dorsal Raphe, Nucleus Accumbens, Caudate Nucleus, and Prefrontal Cortex in Regulating Response to Methylphenidate: Insights from Neuronal and Behavioral Studies in Freely Behaving Rats

Differential Roles of Key Brain Regions: Ventral Tegmental Area, Locus Coeruleus, Dorsal Raphe, Nucleus Accumbens, Caudate Nucleus, and Prefrontal Cortex in Regulating Response to Methylphenidate: Insights from Neuronal and Behavioral Studies in Freely Behaving Rats

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 potential role of stimulants in treating eating disorders

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