Brain dysfunctions and neurotoxicity induced by psychostimulants in experimental models and humans: an overview of recent findings

Serra, Marcello; Simola, Nicola; Pollack, Alexia E.; Costa, Giulia

doi:10.4103/1673-5374.390971

Cited by 3 publications

(1 citation statement)

References 207 publications

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“…Alongside cocaine, amphetamine (AMPH) and its derivatives including 3,4-methylenedioxymethamphetamine (MDMA) are widely recognized as some of the most misused psychostimulants, especially among adolescents. These substances trigger an excessive release of monoamines at the synaptic level by binding membrane-located transporters of dopamine [ 61 ], norepinephrine, and serotonin [ 62 ] but also lead to a sustained rise in glutamate, leading to neurotoxicity [ 63 ]. Studies on rats showed that repeated exposure to methamphetamine augmented glutamate levels within various brain regions including the striatum [ 64 ], hippocampus [ 65 ], VTA [ 66 ], nucleus accumbens, and PFC [ 67 ].…”

Section: Involvement Of Glutamate Excitotoxicity In Substance Use Dis...mentioning

confidence: 99%

Glutamate-Mediated Excitotoxicity in the Pathogenesis and Treatment of Neurodevelopmental and Adult Mental Disorders

Nicosia,

Giovenzana,

Misztak

et al. 2024

IJMS

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Glutamate is the main excitatory neurotransmitter in the brain wherein it controls cognitive functional domains and mood. Indeed, brain areas involved in memory formation and consolidation as well as in fear and emotional processing, such as the hippocampus, prefrontal cortex, and amygdala, are predominantly glutamatergic. To ensure the physiological activity of the brain, glutamatergic transmission is finely tuned at synaptic sites. Disruption of the mechanisms responsible for glutamate homeostasis may result in the accumulation of excessive glutamate levels, which in turn leads to increased calcium levels, mitochondrial abnormalities, oxidative stress, and eventually cell atrophy and death. This condition is known as glutamate-induced excitotoxicity and is considered as a pathogenic mechanism in several diseases of the central nervous system, including neurodevelopmental, substance abuse, and psychiatric disorders. On the other hand, these disorders share neuroplasticity impairments in glutamatergic brain areas, which are accompanied by structural remodeling of glutamatergic neurons. In the current narrative review, we will summarize the role of glutamate-induced excitotoxicity in both the pathophysiology and therapeutic interventions of neurodevelopmental and adult mental diseases with a focus on autism spectrum disorders, substance abuse, and psychiatric disorders. Indeed, glutamatergic drugs are under preclinical and clinical development for the treatment of different mental diseases that share glutamatergic neuroplasticity dysfunctions. Although clinical evidence is still limited and more studies are required, the regulation of glutamate homeostasis is attracting attention as a potential crucial target for the control of brain diseases.

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Section: Involvement Of Glutamate Excitotoxicity In Substance Use Dis...mentioning

confidence: 99%

Glutamate-Mediated Excitotoxicity in the Pathogenesis and Treatment of Neurodevelopmental and Adult Mental Disorders

Nicosia,

Giovenzana,

Misztak

et al. 2024

IJMS

View full text Add to dashboard Cite

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Malignant Catatonia in the Setting of Acute Methamphetamine and Cocaine Intoxication

Mullen,

Meyer Karre,

Balasanova

2024

J Addict Med

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Background Malignant catatonia is a potentially lethal neuropsychiatric syndrome characterized by psychomotor abnormalities and autonomic instability. Patients with this syndrome require immediate treatment. Various psychiatric conditions and nonpsychiatric medical problems can trigger malignant catatonia. Use of psychostimulant drugs, including methamphetamine and cocaine, has not been previously reported to precipitate malignant catatonia. Case Summary This case concerns a 35-year-old man hospitalized for psychosis due to methamphetamine and cocaine intoxication. He developed malignant catatonia the day after admission. He was treated with lorazepam for malignant catatonia, and his blood pressure was controlled with clonidine. Over 7 days, his condition resolved, and his mental status and vital signs returned to baseline. He was discharged to the community in stable condition and has returned to his baseline functional status. He remains free of catatonia and has maintained abstinence from methamphetamine and cocaine. Conclusions Acute intoxication with psychostimulant drugs is a possible trigger for malignant catatonia, and administration of high potency first-generation antipsychotics in this setting may increase the risk. Patients hospitalized for stimulant intoxication should be monitored for signs and symptoms of catatonia, and D2 receptor antagonist medications should be used with caution in this population. Our case supports the potential role of altered dopamine and norepinephrine signaling in the pathogenesis of malignant catatonia. The patient provided written and verbal consent to publish the information in this case report.

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Amphetamine and methylphenidate potential on the recovery from stroke and traumatic brain injury: a review

Ferreira,

Carneiro,

Costa

et al. 2024

Reviews in the Neurosciences

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The prevalence of stroke and traumatic brain injury is increasing worldwide. However, current treatments do not fully cure or stop their progression, acting mostly on symptoms. Amphetamine and methylphenidate are stimulants already approved for attention deficit hyperactivity disorder and narcolepsy treatment, with neuroprotective potential and benefits when used in appropriate doses. This review aimed to summarize pre-clinical and clinical trials testing either amphetamine or methylphenidate for the treatment of stroke and traumatic brain injury. We used PubMed as a database and included the following keywords ((methylphenidate) OR (Ritalin) OR (Concerta) OR (Biphentin) OR (amphetamine) OR (Adderall)) AND ((stroke) OR (brain injury) OR (neuroplasticity)). Overall, studies provided inconsistent results regarding cognitive and motor function. Neurite outgrowth, synaptic proteins, dendritic complexity, and synaptic plasticity increases were reported in pre-clinical studies along with function improvement. Clinical trials have demonstrated that, depending on the brain region, there is an increase in motor activity, attention, and memory due to the stimulation of the functionally depressed catecholamine system and the activation of neuronal remodeling proteins. Nevertheless, more clinical trials and pre-clinical studies are needed to understand the drugs’ full potential for their use in these brain diseases namely, to ascertain the treatment time window, ideal dosage, long-term effects, and mechanisms, while avoiding their addictive potential.

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Brain dysfunctions and neurotoxicity induced by psychostimulants in experimental models and humans: an overview of recent findings

Cited by 3 publications

References 207 publications

Glutamate-Mediated Excitotoxicity in the Pathogenesis and Treatment of Neurodevelopmental and Adult Mental Disorders

Glutamate-Mediated Excitotoxicity in the Pathogenesis and Treatment of Neurodevelopmental and Adult Mental Disorders

Malignant Catatonia in the Setting of Acute Methamphetamine and Cocaine Intoxication

Amphetamine and methylphenidate potential on the recovery from stroke and traumatic brain injury: a review

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