Isradipine Enhancement of Cerebral Blood Flow in Abstinent Cocaine Abusers with and without Chronic Perfusion Deficits

Gottschalk, Paola; Kosten, Thomas R.

doi:10.1080/10550490290087983

Cited by 16 publications

(20 citation statements)

References 20 publications

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“…Therefore, the observed antioxidant defense decrease could be due to other origins. Cocaine-induced vasoconstriction may decreases cerebellar blood flow, leading to hypoxia increasing ROS ( Kaufman et al, 1998 ; Gottschalk and Kosten, 2002 ; Pae et al, 2005 ). Additionally, it has been described that cocaine increases brain temperature, which is a reliable indicator of metabolic neural activation ( Kiyatkin and Brown, 2004 ) and thus, cocaine-enhanced metabolism can increase ROS ( Brookes et al, 2004 ).…”

Section: Discussionmentioning

confidence: 99%

Cocaine promotes oxidative stress and microglial-macrophage activation in rat cerebellum

López‐Pedrajas

Ramírez-Lamelas

Muriach

et al. 2015

Front. Cell. Neurosci.

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Different mechanisms have been suggested for cocaine neurotoxicity, including oxidative stress alterations. Nuclear factor kappa B (NF-κB), considered a sensor of oxidative stress and inflammation, is involved in drug toxicity and addiction. NF-κB is a key mediator for immune responses that induces microglial/macrophage activation under inflammatory processes and neuronal injury/degeneration. Although cerebellum is commonly associated to motor control, muscular tone, and balance. Its relation with addiction is getting relevance, being associated to compulsive and perseverative behaviors. Some reports indicate that cerebellar microglial activation induced by cannabis or ethanol, promote cerebellar alterations and these alterations could be associated to addictive-related behaviors. After considering the effects of some drugs on cerebellum, the aim of the present work analyzes pro-inflammatory changes after cocaine exposure. Rats received daily 15 mg/kg cocaine i.p., for 18 days. Reduced and oxidized forms of glutathione (GSH) and oxidized glutathione (GSSG), glutathione peroxidase (GPx) activity and glutamate were determined in cerebellar homogenates. NF-κB activity, CD68, and GFAP expression were determined. Cerebellar GPx activity and GSH/GSSG ratio are significantly decreased after cocaine exposure. A significant increase of glutamate concentration is also observed. Interestingly, increased NF-κB activity is also accompanied by an increased expression of the lysosomal mononuclear phagocytic marker ED1 without GFAP alterations. Current trends in addiction biology are focusing on the role of cerebellum on addictive behaviors. Cocaine-induced cerebellar changes described herein fit with previosus data showing cerebellar alterations on addict subjects and support the proposed role of cerebelum in addiction.

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Section: Discussionmentioning

confidence: 99%

Cocaine promotes oxidative stress and microglial-macrophage activation in rat cerebellum

López‐Pedrajas

Ramírez-Lamelas

Muriach

et al. 2015

Front. Cell. Neurosci.

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“…As summarized in Table III, conflicting results have been reported in preliminary clinical studies examining stimulants' abuse liability in humans [Muntaner et al, 1991;Rosse et al, 1994;Fabian and Silverstone, 1997;Johnson et al, 1999Johnson et al, , 2004Johnson et al, , 2005bMalcolm et al, 1999;Gottschalk and Kosten, 2002;Sofuoglu et al, 2003;Roache et al, 2005]. Roache et al [2005] suggested that isradipine could even increase subjective effects and reinforcement caused by cocaine use.…”

Section: Psychostimulantsmentioning

confidence: 92%

“…In particular, in animals, isradipine showed the greatest anti-ischemic effectiveness in comparison with other calcium-channel antagonists and has been suggested as a therapeutic agent to counteract cocaine-related vasospasm and stroke [Johnson et al, 2001]. Nimodipine not superior to P in reducing craving Rosse et al [1994] Diltiazem 60 mg Pre-treatment with Isradipine attenuated some of the subjective effects and craving for d-amphetamine Johnson et al [1999] Isradipine 15 mg 6 15 cocaine-dependent subjects (6 with CBF deficits, 9 without deficits) and 20 controls OL, SPECT imaging on admission and after 48 h of Isradipine treatment to measure cerebral blood flow Increased CBF in discrete areas Gottschalk and Kosten [2002] Isradipine 10 mg, Naltrexone 50 mg 9…”

Section: Neurodegenerative Disorders Learning and Memorymentioning

confidence: 99%

L‐type calcium channels and psychiatric disorders: A brief review

Casamassima

Hay

Benedetti

et al. 2010

American J of Med Genetics Pt B

116

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Emerging evidence from genome-wide association studies (GWAS) support the association of polymorphisms in the alpha 1C subunit of the L-type voltage-gated calcium channel gene (CACNA1C) with bipolar disorder. These studies extend a rich prior literature implicating dysfunction of L-type calcium channels (LTCCs) in the pathophysiology of neuropsychiatric disorders. Moreover, calcium channel blockers reduce Ca(2+) flux by binding to the α1 subunit of the LTCC and are used extensively for treating hypertension, preventing angina, cardiac arrhythmias and stroke. Calcium channel blockers have also been studied clinically in psychiatric conditions such as mood disorders and substance abuse/dependence, yielding conflicting results. In this review, we begin with a summary of LTCC pharmacology. For each category of disorder, this article then provides a review of animal and human data. In particular, we extensively focus on animal models of depression and clinical trials in mood disorders and substance abuse/dependence. Through examining rationale and study design of published clinical trials, we provide some of the possible reasons why we still do not have definitive evidence of efficacy of calcium-channel antagonists for mood disorders. Refinement of genetic results and target phenotypes, enrollment of adequate sample sizes in clinical trials and progress in physiologic and pharmacologic studies to synthesize tissue and isoform specific calcium channel antagonists, are all future challenges of research in this promising field. © 2010 Wiley-Liss, Inc.

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“…Fourteen healthy normal control subjects were obtained from a database of repeated SPECT scans acquired on different days, as described previously (18,39). Thus in the normal subjects, as in the patients, two scans were obtained for each individual.…”

Section: Methodsmentioning

confidence: 99%