RESUMEN
Pharmacological magnetic resonance imaging (phMRI) maps the neurovascular response to a pharmacological challenge and is increasingly used to assess neurotransmitter systems. Here we investigated the hemodynamic response to a dopaminergic (DAergic) challenge with dextroamphetamine (dAMPH) in humans using arterial spin labeling (ASL) based phMRI. Twelve healthy male subjects aged 21.0years (±1.5) were included. We used a pseudo-continuous ASL sequence (40min) to quantify cerebral blood flow (CBF) and started dAMPH infusion (0.3mg/kg) after 10min. On another day, we measured baseline dopamine D2/3 receptor availability with [(123)I]IBZM single photon emission computed tomography (SPECT). Baseline measures on mood and impulsivity and subjective behavioral responses to dAMPH were obtained. CBF response was corrected for cardiovascular effects using an occipital cortex mask for internal reference. Corrected CBF (sCBF) was analyzed using ROI-based and voxel-based analysis, in addition to independent component analysis (ICA). CBF data was correlated to D2/3 receptor availability and behavioral measures. Subjects reported experiencing euphoria following dAMPH administration. In the striatum sCBF significantly increased, as demonstrated by all three analysis methods. Voxel-based analysis and ICA also showed increased sCBF in the thalamus, anterior cingulate and cerebellum. Decreased sCBF was observed in several cortical areas, the posterior cingulated and paracingulate cortex. Apart from one ICA component, no correlations were found with sCBF changes and D2/3 receptor availability and behavioral measures. Our observations are in line with literature and provide further evidence that ASL-based phMRI with dAMPH is a promising technique to assess DAergic function in human subjects.
Asunto(s)
Mapeo Encefálico/métodos , Encéfalo/irrigación sanguínea , Estimulantes del Sistema Nervioso Central/farmacología , Dextroanfetamina/farmacología , Dopamina/metabolismo , Imagen por Resonancia Magnética/métodos , Encéfalo/efectos de los fármacos , Circulación Cerebrovascular/efectos de los fármacos , Circulación Cerebrovascular/fisiología , Hemodinámica , Humanos , Masculino , Receptores de Dopamina D2/metabolismo , Receptores de Dopamina D3/metabolismo , Marcadores de Spin , Tomografía Computarizada de Emisión de Fotón Único , Adulto JovenRESUMEN
BACKGROUND: Neuroimaging studies have demonstrated gray matter (GM) volume abnormalities in substance users. While the majority of substance users are polysubstance users, very little is known about the relation between GM volume abnormalities and polysubstance use. METHODS: In this study we assessed the relation between GM volume, and the use of alcohol, tobacco, cocaine and cannabis as well as the total number of substances used, in a sample of 169 males: 15 non-substance users, 89 moderate drinkers, 27 moderate drinkers who also smoke tobacco, 13 moderate drinkers who also smoke tobacco and use cocaine, 10 heavy drinkers who smoke tobacco and use cocaine and 15 heavy drinkers who smoke tobacco, cannabis and use cocaine. RESULTS: Regression analyses showed that there was a negative relation between the number of substances used and volume of the dorsal medial prefrontal cortex (mPFC) and the ventral mPFC. Without controlling for the use of other substances, the volume of the dorsal mPFC was negatively associated with the use of alcohol, tobacco, and cocaine. After controlling for the use of other substances, a negative relation was found between tobacco and cocaine and volume of the thalami and ventrolateral PFC, respectively. CONCLUSION: These findings indicate that mPFC alterations may not be substance-specific, but rather related to the number of substances used, whereas, thalamic and ventrolateral PFC pathology is specifically associated with tobacco and cocaine use, respectively. These findings are important, as the differential alterations in GM volume may underlie different cognitive deficits associated with substance use disorders.
Asunto(s)
Alcoholismo/diagnóstico por imagen , Trastornos Relacionados con Cocaína/diagnóstico por imagen , Sustancia Gris/diagnóstico por imagen , Abuso de Marihuana/diagnóstico por imagen , Autoinforme , Tabaquismo/diagnóstico por imagen , Adolescente , Adulto , Consumo de Bebidas Alcohólicas/efectos adversos , Consumo de Bebidas Alcohólicas/epidemiología , Consumo de Bebidas Alcohólicas/tendencias , Alcoholismo/epidemiología , Cannabis/efectos adversos , Cocaína/administración & dosificación , Cocaína/efectos adversos , Trastornos Relacionados con Cocaína/epidemiología , Consumidores de Drogas , Etanol/administración & dosificación , Etanol/efectos adversos , Sustancia Gris/efectos de los fármacos , Humanos , Imagen por Resonancia Magnética/tendencias , Masculino , Abuso de Marihuana/epidemiología , Persona de Mediana Edad , Neuroimagen/tendencias , Tamaño de los Órganos , Trastornos Relacionados con Sustancias/diagnóstico por imagen , Trastornos Relacionados con Sustancias/epidemiología , Nicotiana/efectos adversos , Uso de Tabaco/epidemiología , Uso de Tabaco/tendencias , Tabaquismo/epidemiología , Adulto JovenRESUMEN
Using data form a 14-day double-blind trial with 48 smokers randomized to either N-acetylcysteine (2400 mg) or placebo, we tested the effect of N-acetylcysteine on glutamate and gamma-aminobutyric acid concentrations in the dorsal anterior cingulate cortex and on smoking cessation. Smoking related behaviors and neurotransmitter concentrations in the dorsal anterior cingulate cortex were assessed before and after treatment. Forty-seven non-smoking males served as baseline controls. Smokers showed higher baseline glutamate but similar gamma-aminobutyric acid concentrations than non-smokers. There were no treatment effects on dorsal anterior cingulate cortex neurotransmitter concentrations, smoking cessation, craving, or withdrawal symptoms. These results confirm glutamate disbalance in smokers, but not efficacy of N-acetylcysteine.
Asunto(s)
Acetilcisteína/uso terapéutico , Ácido Glutámico/metabolismo , Giro del Cíngulo/efectos de los fármacos , Síndrome de Abstinencia a Sustancias/tratamiento farmacológico , Síndrome de Abstinencia a Sustancias/metabolismo , Tabaquismo/tratamiento farmacológico , Ácido gamma-Aminobutírico/metabolismo , Adulto , Ansia/efectos de los fármacos , Método Doble Ciego , Giro del Cíngulo/metabolismo , Humanos , Masculino , Cese del Hábito de Fumar/métodos , Tabaquismo/metabolismoRESUMEN
BACKGROUND: Dopamine (DA) is involved in systems governing motor actions, motivational processes and cognitive functions. Preclinical studies have shown that even relatively low doses of d-amphetamine (dAMPH) (equivalent to doses used in clinical Practice) can lead to DA neurotoxicity in rodents and non-human primates (Ricaurte et al., 2005). METHODS: Therefore, we investigated the DAergic function in eight male recreational users of dAMPH and eight male healthy controls using functional magnetic resonance imaging (fMRI). We compared brain activation between both groups during a monetary incentive delay task (Knutson et al., 2001) with and without an oral methylphenidate (MPH) challenge. All subjects were abstinent for at least 2 weeks during the baseline scan. The second scan was performed on the same day 1.5 h after receiving an oral dose of 35 mg MPH (approximately 0.5 mg/kg) when peak MPH binding was assumed. RESULTS: When anticipating reward, dAMPH users showed lower striatal activation in comparison to control subjects. In addition, MPH induced a reduction in the striatal activation during reward anticipation in healthy controls, whereas no such effect was observed in dAMPH users. CONCLUSION: The combination of these findings provides further evidence for frontostriatal DAergic dysfunction in recreational dAMPH users and is consistent with preclinical data suggesting neurotoxic effects of chronic dAMPH use. The findings of this explorative study could have important implications for humans in need for treatment with dAMPH, such as patients suffering from ADHD and therefore this study needs replication in a larger sample.