Striatal dopamine, dopamine transporter, and vesicular monoamine transporter in chronic cocaine users.
ABSTRACT Depletion of striatal dopamine (DA) has been hypothesized to explain some of the neurological and psychiatric complications of chronic use of cocaine, including increased risk for neuroleptic-precipitated movement disorders. We measured levels of DA, as well as two DA nerve terminal indices, namely, the DA transporter (DAT) and the vesicular monoamine transporter (VMAT2) in autopsied brain of 12 chronic cocaine users. Mean DA levels were normal in the putamen, the motor component of the striatum; however 4 of the 12 subjects had DA values below the lower limit of the control range. DA concentrations were significantly reduced in the caudate head (head, -33%; tail, -39%) with a trend for reduction in nucleus accumbens (-27%). Striatal DAT protein (-25 to -46%) and VMAT2 (-17 to -22%) were reduced, whereas DAT determined by [3H]WIN 35,428 binding was normal. In conclusion, our data suggest that chronic cocaine use is associated with modestly reduced levels of striatal DA and the DA transporter in some subjects and that these changes might contribute to the neurological and psychiatric effects of the drug.
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ABSTRACT: Introduction: There are no FDA-approved pharmacotherapies for treating cocaine addiction; thus, developing drugs to treat cocaine dependence is an unmet critical need. Fortunately, there are a number of drugs that are currently in Phase II clinical trial/s. This is due in part to the advances from in vivo imaging in humans which provided a roadmap of the neurochemistry of the cocaine-dependent brain. Most drugs currently in Phase II clinical trials attempt to modulate the disturbed neurochemistry in cocaine dependents to resemble those of healthy individuals. These predominantly modulate dopamine, serotonin, glutamate, GABA or noradrenaline signalling. Areas covered: This review summarizes the therapeutic potential of each drug as evidenced by clinical and preclinical studies. It also discusses their utility in terms of bioavailability and half-life. Expert opinion: Amphetamine salts and topiramate clearly stand out in terms of their potential efficacy in treating cocaine addiction. The efficacy of topiramate was closely associated with regular cognitive-behavioural therapy (CBT), which highlights the importance of a combined effort to promote abstinence and enhance retention via CBT. Cognitive/psychological screening appears necessary for a more symptom-based approach with more reasonable outcomes other than abstinence (e.g., improved quality of life) in treating cocaine addiction.Expert Opinion on Investigational Drugs 04/2014; · 4.74 Impact Factor
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ABSTRACT: Illicit psychostimulant addiction remains a significant problem worldwide, despite decades of research into the neural underpinnings and various treatment approaches. The purpose of this review is to provide a succinct overview of the neurocircuitry involved in drug addiction, as well as the acute and chronic effects of cocaine and amphetamines within this circuitry in humans. Investigational pharmacological treatments for illicit psychostimulant addiction are also reviewed. Our current knowledge base clearly demonstrates that illicit psychostimulants produce lasting adaptive neural and behavioral changes that contribute to the progression and maintenance of addiction. However, attempts at generating pharmacological treatments for psychostimulant addiction have historically focused on intervening at the level of the acute effects of these drugs. The lack of approved pharmacological treatments for psychostimulant addiction highlights the need for new treatment strategies, especially those that prevent or ameliorate the adaptive neural, cognitive, and behavioral changes caused by chronic use of this class of illicit drugs.Substance abuse and rehabilitation. 01/2013; 4:29-43.
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ABSTRACT: Animal models of mania lack genuine cognitive parameters. The present gold standard of mania models, amphetamine-induced hyperlocomotion, is rather unspecific and does not necessarily target its cardinal symptoms. Therefore, alternative behavioral markers that are sensitive to stimulants are required.Psychopharmacology 08/2014; · 3.99 Impact Factor