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.
SourceAvailable from: Peter Robert Martin01/2001; Marcel Dekker, Inc.
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ABSTRACT: There is evidence that abnormalities in the dopaminergic system involving the dopamine transporter (DAT) are involved in the pathophysiology of Tourette's disorder (TD) from previous studies using [123I]2β-carbomethoxy-3-(4-iodophenyl)tropane ([123I]β-CIT) and single photon emission tomography (SPECT). However, because those studies were performed in medicated adult patients with TD, we decided to compare DAT densities in nine drug-naive children with TD and eight normal children. The children with TD did not suffer from associated psychiatric problems such as obsessive–compulsive symptoms, attention deficit hyperactivity disorder, anxiety, depression and developmental difficulties. We performed brain SPECT 2 h after the intravenous administration of I-123N-(3-iodopropen-2-yl)-2β-carbomethoxy-3beta-(4-chlorophenyl)tropane ([123I]IPT) and carried out both quantitative and qualitative analyses using the obtained SPECT data, which were reconstructed for the assessment of the specific/non-specific DAT binding ratio in the basal ganglia. We then investigated the correlation between the severity of tics in children with TD assessed with the Yale Global Tic Severity Scale (YGTSS) and the specific/non-specific DAT binding ratio of the basal ganglia. Drug-naive children with TD showed a significantly increased specific/non-specific DAT binding ratio in the basal ganglia compared with normal children that did not correlate significantly with the severity of tics. Our results with drug-naive children with TD between the ages of 6 and 12 may help to clarify previous findings concerning DAT binding in adult patients with TD and suggest that DAT densities may be associated directly with the pathophysiology of TD, regardless of disease progress or drug effect.Psychiatry Research Neuroimaging 01/2003; DOI:10.1016/S0925-4927(03)00138-0 · 2.83 Impact Factor
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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. In the present study, by combining the psychostimulant-induced model of mania in rodents with the recently developed ambiguous-cue interpretation (ACI) tests, we investigated the effects of chronic administration of d-amphetamine and cocaine on the cognitive judgment bias of rats. To accomplish this goal, in two separate experiments, previously trained animals received chronic, daily injections of either d-amphetamine (2 mg/kg) or cocaine (10 mg/kg) for 2 weeks and were subsequently tested with the ACI procedure. Chronic treatment with both psychostimulants did not make rats more "optimistic." The results are discussed in terms of behavioral and pharmacological actions of the tested compounds and their implications for modeling mania in animals.Psychopharmacology 08/2014; 232(3). DOI:10.1007/s00213-014-3707-y · 3.99 Impact Factor