Reduction in dopamine transporter mRNA after cessation of repeated cocaine administration

Cerruti, Catherine; Pilotte, Nancy S.; Uhl, George R.; Kuhar, Michael J.

doi:10.1016/0169-328x(94)90040-x

Cited by 89 publications

(45 citation statements)

References 44 publications

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“…This support notwithstanding, it must be recognized that decreases in DAT density could be related to a neuroadaptive process, perhaps compensating for a depletion of brain DA not associated with actual DA nerve terminal degeneration. Indeed, there are several reports of changes in DAT density after a variety of pharmacological manipulations that do not involve DA neurotoxicity (Cerruti et al, 1994;Koff et al, 1994;Tella et al, 1997;Malison et al, 1998). To our knowledge, however, none of the reported changes in DAT density are in the direction or as long-lasting as the reductions herein documented.…”

Section: Discussionmentioning

confidence: 99%

Reduced Striatal Dopamine Transporter Density in Abstinent Methamphetamine and Methcathinone Users: Evidence from Positron Emission Tomography Studies with [¹¹C]WIN-35,428

et al. 1998

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Methamphetamine and methcathinone are psychostimulant drugs with high potential for abuse. In animals, methamphetamine and related drugs are known to damage brain dopamine (DA) neurons, and this damage has recently been shown to be detectable in living nonhuman primates by means of positron emission tomography (PET) with [11 C]WIN-35,428, a DA transporter (DAT) ligand. The present studies determined whether living humans with a history of methamphetamine or methcathinone abuse showed evidence of lasting decrements in brain DAT density. PET studies were performed in 10 control subjects, six abstinent methamphetamine users, four abstinent methcathinone users, and three patients with Parkinson's disease (PD). On average, subjects had abstained from amphetamine use for ϳ3 years. Before PET studies, all subjects underwent urine and blood toxicology screens to rule out recent drug use. Compared with controls, abstinent methamphetamine and methcathinone users had significant decreases in DAT density in the caudate nucleus (Ϫ23 and Ϫ24%, respectively) and putamen (Ϫ25 and Ϫ16%, respectively). Larger decreases in DAT density were evident in patients with PD (47 and 68% in caudate and putamen, respectively). Neither methamphetamine nor methcathinone users showed clinical signs of parkinsonism. Persistent reductions of DAT density in methamphetamine and methcathinone users are suggestive of loss of DAT or loss of DA terminals and raise the possibility that as these individuals age, they may be at increased risk for the development of parkinsonism or neuropsychiatric conditions in which brain DA neurons have been implicated.

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Section: Discussionmentioning

confidence: 99%

Reduced Striatal Dopamine Transporter Density in Abstinent Methamphetamine and Methcathinone Users: Evidence from Positron Emission Tomography Studies with [¹¹C]WIN-35,428

et al. 1998

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“…In experiments that depend on binding as an index of neuronal density, one potential difficulty that could lead to an erroneous interpretation of the findings is the up-or downregulation of transporter sites occurring in response to the changing synaptic levels of DA (32,38). From (33,34).…”

Section: Discussionmentioning

confidence: 99%

Dopamine transporters are markedly reduced in Lesch-Nyhan disease in vivo.

Wong

Harris

Naidu

et al. 1996

Proc. Natl. Acad. Sci. U.S.A.

205

107

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Dopamine (DA) deficiency has been implicated in Lesch-Nyhan disease (LND), a genetic disorder that is characterized by hyperuricemia, choreoathetosis, dystonia, and compulsive self-injury. To Several neurodevelopmental disorders are thought to involve the neuropathology of the basal ganglia. Among them, the best known are Lesch-Nyhan disease (LND) and Rett syndrome. In both of these conditions, there is evidence for the dysfunction of the dopaminergic neurotransmission.LND is an X-chromosome-linked disease with infantile onset characterized by hyperuricemia, choreoathetosis, dystonia, and compulsive self-injury (1). The underlying defect is a near absence of hypoxanthine-guanine phosphoribosyl transferase (HPRT) (2), an enzyme that is normally present in the brain in greater amounts than in other organs. Three lines of evidence suggest that HPRT deficiency is linked to abnormal dopamine (DA) function in LND: (i) an autopsy study of three LND subjects demonstrated a marked reduction in the DA content and in the activity of DA-synthesizing enzymes in the caudate and putamen (3); (ii) when neonatal rats are depleted of DA with the neurotoxin 6-hydroxydopamine, self-injurious behavior (similar to that seen in LND) occurs when the rats are challenged with 3,4-dihydroxyphenylalanine (L-dopa) as adults (4, 5); and (iii) in an HPRT-deficient mutant mouse strain, there is a reduction of striatal tyrosine hydroxylase and in the number of striatal dopamine transporters measured with 3H-N-[1-(2-benzo(,B)thiophenyl) cyclohexyl]piperidine (3H-BTCP) (6). The pertinence of the loss of brain DA in LND has been questioned due to the limited scope of the autopsy study and the fact that the HPRT-deficient mouse study showed only a modest reduction of DA with no self-injury, or other clinical symptoms of LND (6). Therefore the question of dopamine reduction in vivo remains unresolved.The availability of positron emission tomography (PET) ligands that bind to pre-or postsynaptic DA sites has made it possible to study the DA system in vivo in patients affected with disorders that involve the basal ganglia. For example, the DA transporter probe ,3-carbomethoxy-3,3-4-fluorophenyl-tropane (CFT; WIN-35,428) (7-11) has been used to detect the degeneration of DA nerve terminals in adult humans (12,13). It has also been used to measure the degeneration of nerve terminals in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated primates and in idiopathic Parkinson disease (14-16). In addition, 428 is suitable for evaluating the integrity of DAcontaining neurons in neurodevelopmental disorders.In the present investigation, the hypothesis-that HPRT deficiency in LND is associated with impaired development of dopaminergic projections to the striatum-was tested by determining the number of DA transporters in vivo by using PET with the radiolabeled DA transporter ligand 428. The measurement of the presynaptic DA sites of 428 using PET provides a relevant assessment of the degree of dopaminergic deficiency in LND.The binding of [1...

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“…Yet another study found increased DAT binding in the striatum, but not in the nucleus accumbens, after 3 days of withdrawal from repeated cocaine (Claye et al, 1995). After withdrawal from chronic cocaine, DAT mRNA levels in the VTA were decreased in one study (Cerruti et al, 1994) but increased (Arroyo et al, 2000) in another study and unchanged in a third study (Maggos et al, 1997). DAT mRNA levels were unchanged in the substantia nigra (Xia et al, 1992;Arroyo et al, 2000) after withdrawal from chronic cocaine treatment.…”

mentioning

confidence: 96%

“…Again, these reported changes have been inconsistent. A 10-to 14-day withdrawal period after repeated cocaine administration resulted in a decrease in binding to DAT protein in the nucleus accumbens but not in the striatum (Cerruti et al, 1994;Boulay et al, 1996) or in the substantia nigra (Xia et al, 1992). Yet another study found increased DAT binding in the striatum, but not in the nucleus accumbens, after 3 days of withdrawal from repeated cocaine (Claye et al, 1995).…”

mentioning

confidence: 99%

Withdrawal from Repeated Cocaine Alters Dopamine Transporter Protein Turnover in the Rat Striatum

Kimmel¹,

Carroll²,

Kuhar³

2003

J Pharmacol Exp Ther

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Several studies have shown that repeated cocaine administration, followed by withdrawal, alters dopamine transporter (DAT) levels in the rat. These changes must arise from changes in either transporter protein production or degradation, or both. Previously, our laboratory developed an approach to measure the synthesis rate, degradation rate constant, and half-life of DAT in the rat striatum and nucleus accumbens after administration of the irreversible dopamine transporter ligand, RTI-76. These initial studies showed that: 1) the half-life of the transporter was between 2 and 3 days in these two brain regions; 2) pretreatment with dopamine D1 and D2 receptor agonists and antagonists over several days differentially altered DAT half-lives in the striatum and nucleus accumbens; and 3) pretreatment with cocaine for several days increased the half-life of DAT by decreasing the degradation rate constant in both brain regions. In the present study, we determined that repeated pretreatment (10 days) with 20 mg/kg cocaine (i.p.) and a subsequent withdrawal period (10 days) alters the dopamine transporter turnover in the rat striatum, but not in the nucleus accumbens. Cocaine pretreatment and withdrawal reduced the half-life of the transporter protein from 2.1 days to 0.94 day in the striatum, but did not alter the half-life of 2.2 days in the nucleus accumbens. The results indicate the complex and long-lasting effects of cocaine administration on cellular processes. The mechanism(s) of these effects remains to be elucidated.

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Reduction in dopamine transporter mRNA after cessation of repeated cocaine administration

Cited by 89 publications

References 44 publications

Reduced Striatal Dopamine Transporter Density in Abstinent Methamphetamine and Methcathinone Users: Evidence from Positron Emission Tomography Studies with [¹¹C]WIN-35,428

Reduced Striatal Dopamine Transporter Density in Abstinent Methamphetamine and Methcathinone Users: Evidence from Positron Emission Tomography Studies with [¹¹C]WIN-35,428

Dopamine transporters are markedly reduced in Lesch-Nyhan disease in vivo.

Withdrawal from Repeated Cocaine Alters Dopamine Transporter Protein Turnover in the Rat Striatum

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Reduction in dopamine transporter mRNA after cessation of repeated cocaine administration

Cited by 89 publications

References 44 publications

Reduced Striatal Dopamine Transporter Density in Abstinent Methamphetamine and Methcathinone Users: Evidence from Positron Emission Tomography Studies with [11C]WIN-35,428

Reduced Striatal Dopamine Transporter Density in Abstinent Methamphetamine and Methcathinone Users: Evidence from Positron Emission Tomography Studies with [11C]WIN-35,428

Dopamine transporters are markedly reduced in Lesch-Nyhan disease in vivo.

Withdrawal from Repeated Cocaine Alters Dopamine Transporter Protein Turnover in the Rat Striatum

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Product

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Reduced Striatal Dopamine Transporter Density in Abstinent Methamphetamine and Methcathinone Users: Evidence from Positron Emission Tomography Studies with [¹¹C]WIN-35,428

Reduced Striatal Dopamine Transporter Density in Abstinent Methamphetamine and Methcathinone Users: Evidence from Positron Emission Tomography Studies with [¹¹C]WIN-35,428