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.
To establish whether chronic opiate exposure might impair brain dopaminergic or serotonergic function in humans, we assessed biochemical indices of monoaminergic neurotransmitter activity and integrity in post mortem striatum of nine chronic heroin users and 14 control subjects. Striatal levels of the vesicular monoamine transporter were normal, suggesting that the density of dopamine nerve terminals is not reduced in heroin users. In nucleus accumbens, levels of tyrosine hydroxylase protein (-25%) and those of the dopamine metabolite homovanillic acid (-33%) were reduced significantly together with a trend for decreased dopamine (-32%) An important feature of psychostimulant and opiate drugs of abuse is their ability, upon acute administration, to activate brain dopaminergic neurons as evidenced by increased striatal synaptic concentrations of dopamine (DiChiara 1995). Chronic dopaminergic overactivity caused by drugs of abuse leads to a variety of compensatory changes that could influence behavior of the drug user. Synaptic levels of dopamine are decreased in experimental animals withdrawn from chronic psychostimulants (cf. DiChiara 1995) whereas striatal tissue dopamine levels are reduced in human chronic psychostimulant users: moderately for methamphetamine users (Wilson et al. 1996a) or slightly for cocaine users (Wilson et al. 1996b). These changes could explain the dysphoric anhedonic motivational state during withdrawal to psychostimulant drugs. Both experimental animals and humans (cf. Wilson et al. 1996a,b) exposed to psychostimulants also demonstrate altered striatal levels of the dopamine transporter (DAT), a 24 , NO . 5 component of the dopamine nerve terminal critically involved in regulation of synaptic dopamine levels.Relatively less attention has been focused on longterm effects of opiate drugs of abuse on the dopamine system. In fact, it has been assumed that opiates do not produce "enduring changes" in dopaminergic transmission or cellularity (Rogers et al. 1999). Chronic administration of morphine or heroin to rodents, however, causes decreased striatal concentrations of synaptic dopamine (Acquas et al. 1991;Crippens and Robinson 1994), its biosynthetic enzyme tyrosine hydroxylase (Self et al. 1995) and those of DAT (Simantov 1993). Chronic morphine appears to damage dopaminergic neurons as indicated by impaired axonal transport from the dopamine cell body area of the ventral tegmental area (VTA) to nucleus accumbens, decreased size of dopaminergic cell bodies, and by increased expression in VTA of a marker of injury, glial fibrillary acidic protein (Beitner-Johnson et al. 1992;1993;Self et al. 1995; SklairTavron et al. 1996). As these animal data suggest that opiates might impair, reversibly or irreversibly, brain dopaminergic function in humans, we determined whether concentrations of biochemical markers of dopamine nerve terminal function and integrity are decreased in post mortem striatum (caudate, putamen, nucleus accumbens) of human chronic heroin users. The markers included ...
Animal data have long suggested that an adaptive upregulation of nucleus accumbens dopamine D1 receptor function might underlie part of the dependency on drugs of abuse. We measured by quantitative immunoblotting protein levels of dopamine D1 and, for comparison, D2 receptors in brain of chronic users of methamphetamine, cocaine, and heroin. As compared with the controls, brain dopamine D1 receptor concentrations were selectively increased (by 44%) in the nucleus accumbens of the methamphetamine users, whereas a trend was observed in this brain area for reduced protein levels of the dopamine D2 receptor in all three drug groups (؊25 to ؊37%; P < 0.05 for heroin group only). Our data support the hypothesis that aspects of the drug-dependent state in human methamphetamine users might be related to increased dopamine D1 receptor function in limbic brain. Molecular Psychiatry (2000) 5, 664-672.
Clinical, radiographic, surgical, and pathologic findings and survival in 92 patients with diffuse malignant mesothelioma (DMM) of the pleura who were examined at the Mayo Clinic between 1950 and 1980, were studied retrospectively. With the use of defined criteria and ordinary tissue stains, the 92 cases were classified into the following histologic subtypes: purely epithelial, 42 cases; mixed, 29 cases; and sarcomatous, 21 cases. Eight of the sarcomatous cases were desmoplastic. Median survivals were 12, 5, and 3 months for the patients in the epithelial, mixed, and sarcomatous groups, respectively. Survival was significantly longer for patients with epithelial DMM. Women survived longer than men but more often had epithelial DMM. Early disease manifested as multiple discrete pleural nodules, predominantly on the parietal pleura. However, nine patients had a dominant mass. Radiographic signs especially suggestive of DMM were nodular pleural thickening, irregular thickening of interlobar fissures, a dominant mass, or decreased volume of the affected hemithorax.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.