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.

Decreased expression of the transcription factor NURR1 in dopamine neurons of cocaine abusers

“…The cocaine-related reduction in DAT gene expression that we find in the present study is consistent with recent reports associating cocaine abuse or cocaine-induced excited delirium with decreased DAT mRNA (16,17) and DAT protein (18). for study 2).…”

Rapid Recovery of Vesicular Dopamine Levels in Methamphetamine Users in Early Abstinence

“…Results of our autopsied brain and brain PET investigations of 'dopamine' measures are generally similar to the currently reported finding and point to differences in the actions of MA vs cocaine in human brain: MA users having marked differences relative to HC (Moszczynska et al, 2004;Wilson et al, 1996a), whereas cocaine users have, at most, only modest differences (Narendran et al, 2012;Wilson et al, 1996b, see Kish, 2014.…”

Profiles of Cognitive Dysfunction in Chronic Amphetamine and Heroin Abusers

“…It is possible that the reductions in dopamine transporter activity also seen in that group (c.f. Wilson et al 1996b) reflect some of the other impairments seen in this study, for example given significant relationships between striatal dopamine receptor binding and some of the tests (e.g. Tower of London, visuospatial strategy task) and in the present study .…”