Alpha synuclein protein levels are increased in serum from recently abstinent cocaine abusers

Abstract

Alpha synuclein is increased in dopamine neurons of cocaine abusers and in rats whose alcohol preference is inbred. Recent studies have shown increased alpha-synuclein protein expression in serum of alcoholic patients that is linked with severity of alcohol craving. The aim of this study was to analyze the serum levels of alpha synuclein in healthy subjects and in recently abstinent cocaine abusers. Alpha synuclein protein expression was measured by enzyme-linked immunosorbent assay in serum specimens obtained from 38 recently abstinent cocaine dependent patients and 14 control subjects. The presence of cocaine dependence disorder was based on the Structured Clinical Interview (DSM-IV). Drug severity was assessed by the Addiction Severity Index ratings and composite measures. Scores of the intensity and frequency of cocaine craving episodes were obtained from the Minnesota Cocaine Craving Questionnaire. The serum concentrations of alpha synuclein in cocaine dependent patients were significantly higher as compared with age-matched drug-free controls (p < 0.001). Alpha synuclein levels in blood were significantly correlated with the intensity (r = 0.60, p < 0.001) and frequency (r = 0.64. p < 0.001) of cocaine craving and with thirty days of cocaine use in the prior month before entry to treatment (r = 0.56, p < 0.005). However, there was no correlation between the serum protein levels of alpha synuclein and age in either group. This report is the first demonstration of altered alpha synuclein levels in peripheral blood from cocaine abusers. These data agree with previous reports in postmortem brain of cocaine abusers and provide support for an association between alpha synuclein and cocaine dependence.

Parkinsonism and dystonia caused by the illicit use of ephedrone—A longitudinal study

“…Methamphetamine can lead to long-lasting decreases in dopamine and serotoninergic function 13 and increases in alpha synuclein expression have been found in the striatum of cocaine addicts postmortem. 14 However, autopsy studies in young cocaine and crystal Meth addicts have not revealed nigral cell loss. 15 Schmidt et al 1 first reported a patient with severe hypokinesia, pseudobulbar palsy, and pyramidal signs after chronic ephedrone use who failed to respond to anti-Parkinsonian medication, and she speculated that the neurological syndrome was caused by manganese accumulation in the brain.…”

Substance Abuse and Movement Disorders: Complex Interactions and Comorbidities

“…Overexpressed alpha-synuclein has been observed in midbrain dopaminergic neurons from cocaine abusers, possibly representing a neuroadaptive response to the exposure and potentially exposing them at risk for degenerative changes in dopaminergic neurons [40]. In addition, alpha-synuclein protein levels are increased in serum from recently abstinent cocaine abusers [41]. However, unlike methamphetamine or other amphetamine-type drugs, the available evidence suggests it is unlikely that cocaine confers increased risk of PD [42].…”

From QTL to Candidate Gene: A Genetic Approach to Alcoholism Research

“…Likewise, elevated Snca (mRNA, protein) levels were detected in alcoholics [57], and Snca DNA sequence variants have been linked to craving for alcohol in humans [16, 17]. In addition to alcohol-related phenotypes, elevated SNCA levels in midbrain dopaminergic neurons were detected in both cocaine abusers and mice in withdrawal following morphine treatment [58, 59]. Therefore, due to its effects on dopaminergic neurotransmission, Snca is a candidate gene of considerable interest to alcohol-seeking behavior.…”