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David L. Copolov - One of the best experts on this subject based on the ideXlab platform.
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Dopamine Uptake by platelets is selective, temperature dependent and not influenced by the Dopamine-D1 or Dopamine-D2 receptor
Life Sciences, 2002Co-Authors: Brian Dean, David L. CopolovAbstract:Abstract The human platelet, which takes up and releases Dopamine, has been proposed as a peripheral model for the study of Dopaminergic neurons in the central nervous system (CNS). In addition, the platelet has been shown to possess membrane components with pharmacological properties similar to the Dopamine-D1 (DA-D1) and D2 and (DA-D2) receptor on Dopaminergic neurons. We have therefore studied the specificity of the platelet Uptake system for Dopamine and, as Dopamine Uptake comprises both internalised and membrane bound Dopamine, the contribution of the DA-D1 and DA-D2 receptor to the Uptake of Dopamine has been assessed. Significant Uptake of 3H-Dopamine by platelet rich plasma (PRP) occurred after 10 min incubation at 37°C, Uptake being maximal after 90 min. In contrast, at 4°C no Uptake of 3H-Dopamine occurred up to 60 mins incubation but at 20°C was approximately 8% of the 60 min Uptake at 37°C. The neurotransmitters serotonin and Dopamine inhibited Dopamine Uptake by platelets in a dose dependent manner. Uptake of Dopamine appeared to be via two systems, one of high affinity with low capacity and the other of lower affinity but high capacity. In contrast, noradrenaline, adrenaline, acetylcholine, gamma-aminobutyric acid and histamine (10uM) had no effect on Dopamine Uptake by platelets. The DA-D1 receptor antagonist SCH 23390 (10um) and the DA-D2 receptor antagonists (10uM) spiperone, domperidone and (+)-butaclamol did not significantly affect Dopamine Uptake by platelets. In addition, ouabain and desipramine (100uM) inhibited Dopamine Uptake by 21% and 24% respectively whilst reserpine and imipramine (100uM) increased Uptake by 14% and 15%. We therefore conclude that platelets take up Dopamine via a selective, temperature dependent mechanism. Our data also suggest that Dopamine Uptake by platelets does not involve the DA-D1 or DA-D2 receptor.
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Typical and atypical neuroleptic drugs decrease platelet 3H-Dopamine Uptake in the rat
Psychiatry research, 1996Co-Authors: Suresh Sundram, Brian Dean, David L. CopolovAbstract:Reports of opposing changes in platelet 3H-Dopamine Uptake in neuroleptic-free versus neuroleptic-treated schizophrenic subjects have suggested an effect of neuroleptic treatment on this measure. We examined platelet 3H-Dopamine Uptake in rats treated with haloperidol or clozapine to determine if such treatment did affect platelet 3H-Dopamine Uptake. Neuroleptic drug treatment reduced platelet 3H-Dopamine Uptake in a dose- and time-dependent manner. After up to 4 weeks of treatment, these effects were reversed by the discontinuation of neuroleptic drug treatment. These data suggest that the effect of neuroleptic treatment in studies of platelet 3H-Dopamine Uptake could account for the variable findings in schizophrenia.
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Platelet [3H]Dopamine Uptake is differentially affected by neuroleptic drug treatment in schizophrenia and schizophreniform disorder
Progress in Neuro-Psychopharmacology and Biological Psychiatry, 1996Co-Authors: Brian Dean, Suresh Sundram, Christine Hill, David L. CopolovAbstract:Abstract 1. 1. The Uptake of [ 3 H]Dopamine was measured using platelet-rich plasma (PRP) from neurolepticfree subjects and again, in some cases, after the subject had been treated with neuroleptic drugs. 2. 2. There were no differences in [ 3 H]Dopamine Uptake by PRP in subjects who were or were not mentally ill. 3. 3. After treatment with neuroleptic drugs the Km for platelet [ 3 H]Dopamine Uptake had increased in 76% of subjects with schizophrenia and 87% of subjects with Schizophreniform disorder. Similarly, the Vmax for platelet [ 3 H]Dopamine Uptake had increased in 81% of the subjects with schizophrenia and 86% of the subjects with Schizophreniform disorder. 4. 4. By contrast, the Km for platelet [ 3 H]Dopamine Uptake had decreased in 94% of subjects who had a psychoses associated with an illness other than schizophrenia or schizophreniform disorder whilst the Vmax for platelet [ 3 H]Dopamine Uptake also decreased by 94% in these subjects. 5. 5. In subjects with psychoses, platelet [ 3 H]Dopamine Uptake is differentially altered during neuroleptic drug treatment depending on diagnosis.
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The development of a method to measure [3H] Dopamine Uptake by washed platelets provides no evidence for circulating inhibitors of platelet Dopamine Uptake in schizophrenia
Biological psychiatry, 1994Co-Authors: Suresh Sundram, Brian Dean, David L. CopolovAbstract:Altered [3H] Dopamine Uptake by platelet-rich plasma (PRP) has been reported in some subjects with schizophrenia (Rotman et al 1980; Dean et al 1990). As platelet Dopamine Uptake was measured using PRP, it was not possible to determine if the changes in schizophrenia were intrinsic to the platelet or due to plasma factors. Furthermore, the constraints of plasma as a medium for platelet suspension has hindered the study of the physiological requirements of platelet Dopamine Uptake. A method is now reported that allows platelets to be suspended in a controlled medium while preserving the Dopamine Uptake mechanism of the platelet. Dopamine Uptake by platelets in a controlled medium was dependent on temperature, energy, sodium, and chloride. Furthermore, plasma from subjects with schizophrenia and schizophreniform disorder did not significantly alter [3H] Dopamine Uptake by platelets compared to the effect of plasma from control subjects. Hence, these data provide no evidence for a circulating inhibitor of platelet [3H] Dopamine Uptake in plasma from subjects with schizophrenia.
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Dopamine Uptake by platelets from subjects with schizophrenia: a correlation with the delusional state of the patient.
Psychiatry research, 1992Co-Authors: Brian Dean, David L. Copolov, Jayashri Kulkarni, Preethi Shrikanthan, Valcy Malone, Christine HillAbstract:Abstract The Uptake of 3 H-Dopamine by platelets from patients with a number of psychiatric disorders has been compared with that by platelets from normal volunteers. Overall, 3 H-Dopamine Uptake by platelet-rich plasma (PRP) from 25 schizophrenic subjects did not differ from 3 H-Dopamine Uptake by PRP from 22 nonschizophrenic patients and 61 normal volunteers. In the schizophrenic group, however, there was an increased spread of results with seven values falling outside the range of results observed in the control group. Furthermore, of the patients rated, only for the schizophrenic patients was there an inverse correlation between 3 H-Dopamine Uptake by platelets and the rating for delusions on the Scale for the Assessment of Positive Symptoms. Thus, 3 H-Dopamine Uptake by platelets seems, in some way, to be linked to the delusional state of the patient. Further study of 3 H-Dopamine Uptake by platelets is warranted in a larger and more diverse group of patients to determine the significance of altered Dopamine Uptake by platelets from some schizophrenic subjects and the correlation between platelet 3 H-Dopamine Uptake and the delusional state of these subjects.
Jean Costentin - One of the best experts on this subject based on the ideXlab platform.
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Although Chemically Related to Amineptine, the Antidepressant Tianeptine Is Not a Dopamine Uptake Inhibitor
Pharmacology Biochemistry and Behavior, 1999Co-Authors: Jean-marie Vaugeois, A.t Corera, A Deslandes, Jean CostentinAbstract:Abstract We investigated whether the antidepressant tianeptine shares the Dopamine Uptake inhibitory properties of the chemically related antidepressant amineptine. Tianeptine dose dependently (5, 10, 20, 40 mg/kg IP) increased locomotor activity in mice. This stimulant effect (20 mg/kg IP) was dose dependently prevented not only by the D 1 Dopamine receptor antagonist SCH 23390 (7.5, 15, 30 μg/kg SC), but also by the D 2 Dopamine receptor antagonist haloperidol (50, 100, 200 μg/kg IP), in contrast to that elicited by Dopamine Uptake inhibitors. Where the latter prevent dexamphetamine-induced (3 mg/kg SC) reversion of akinesia in mice pretreated with reserpine (4 mg/kg SC, 5 h before test), tianeptine (20 mg/kg IP, 30 min before test) did not. Tested up to a concentration of 10−4 M, tianeptine did neither inhibit the [ 3 H]Dopamine Uptake into mouse striatal synaptosomes nor compete in vitro with the specific binding of [ 3 H]WIN 35,428 at Dopamine transporters from striatal membranes. Finally, in mice injected IV with a tracer dose of [ 3 H]WIN 35,428 (1 μCi), the highest tested dose of tianeptine (40 mg/kg IP) did not reduce the specific binding of the radioligand to striatal Dopamine transporters. It is concluded that the antidepressant effect of tianeptine does not depend upon a blockade of the neuronal Dopamine transporter.
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Behavioural and neurochemical evidence that the antimicrobial agent oxolinic acid is a Dopamine Uptake inhibitor
European Neuropsychopharmacology, 1998Co-Authors: J. Garcia De Mateos-verchere, Bertrand Naudin, Jean-marie Vaugeois, Jean CostentinAbstract:Abstract The antimicrobial agent oxolinic acid, injected i.p. in mice, induced a dose dependent increase in locomotor activity. This stimulation culminated at the 32 mg/kg dose and became smaller for higher doses (64–128 mg/kg). When opposed to increasing doses (50–100–200 μg/kg i.p.) of haloperidol (D2 Dopamine receptor antagonist), the stimulant locomotor effect of 32 mg/kg oxolinic acid was not significantly reversed. On the contrary increasing doses (7.5–15–30 μg/kg s.c.) of SCH 23390 (D1 Dopamine receptor antagonist) inhibited the stimulant locomotor effect. In mice made completely akinetic by a pretreatment with reserpine (4 mg/kg s.c., 18 h before testing), dexamphetamine (2 mg/kg s.c.) reversed this akinesia and even displayed a stimulant activity, similar to that observed in mice not treated by reserpine. On the contrary, oxolinic acid (32 mg/kg) did not reverse the reserpine induced akinesia and even opposed the reversion induced by dexamphetamine. In a synaptosomal fraction prepared from striatum of rats, oxolinic acid inhibited the 3 H Dopamine Uptake with an IC50=4.3±0.6×10−6 M. Finally, in mice injected i.v. with a tracer dose of 3 H WIN 35428 (1 μCi) (a Dopamine Uptake blocker), 32 mg/kg oxolinic acid, i.p. administered, reduced by about 50% the specific binding of the radioligand to striatal Dopamine carriers. It is concluded that the stimulant locomotor effect of oxolinic acid depends on the blockade of the neuronal Dopamine Uptake complex.
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Place conditioning with cocaine and the Dopamine Uptake inhibitor GBR12783.
Neuroreport, 1996Co-Authors: G. Le Pen, D. Duterte-boucher, Jean CostentinAbstract:THE rewarding and locomotor effects of the specific Dopamine Uptake inhibitor GBR12783 (2.5-20mg kg -1 , i.p.) were compared with those of cocaine. For both drugs, all doses produced a conditioned place preference (CPP), even the dose of 2.5 mg kg -1 , which did not modify the locomotor activity. Despite an equivalent locomotor stimulation, the magnitude of CPP induced by cocaine (10 mg kg -1 ) was greater than that induced by the same dose of GBR12783. This confirms the involvement of Dopamine Uptake inhibition in reward, but underlines differences in relative efficacies in rewarding and motor effects of both drugs and suggests that these two properties are, at least in part, separable anatomically or functionally.
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Invariance of the density of Dopamine Uptake sites and Dopamine metabolism in the rat brain after a chronic treatment with the Dopamine Uptake inhibitor GBR 12783.
Journal of neural transmission. General section, 1994Co-Authors: D. Boulay, I. Leroux-nicollet, D. Duterte-boucher, L. Naudon, Jean CostentinAbstract:A chronic treatment (10 mg/kg, twice daily during 9 days) with the Dopamine Uptake inhibitor GBR 12783 was performed in rats at a dose increasing their locomotor activity.
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In vivo labelling of the neuronal Dopamine Uptake complex in the mouse striatum by [3H]GBR 12783.
European journal of pharmacology, 1992Co-Authors: Jean-marie Vaugeois, J.-j. Bonnet, Jean CostentinAbstract:Abstract Various characteristics of the in vivo striatal binding of [ 3 H]GBR 12783 (1-[2-(diphenylmethoxy)-ethyl]-4-(3-phenyl-1[ 3 H]-2- propenyl)piperazine), a specific ligand of the neuronal Dopamine Uptake complex, were determined in mice. Increasing doses of the ligand revealed the saturability of the binding at a single site with half-maximal saturation at a dose of approximately 7 ωmol/kg and an apparent maximal number of binding sites (B max ) of 12.8 pmol/mg protein in striatum. Specific binding was prevented by various Dopamine Uptake blockers, pyrovalerone, GBR 13069, GBR 12783, N-[1-2-benzo(b)thiophenyl)cyclohexyl] piperidine, cocaine, methylphenidate and was inhibited in a stereoselective manner by the enantiomers of nomifensine. Other drugs which are not Dopamine Uptake blockers either did not modify [ 3 H]GBR 12783 binding (the diphenylbutylpiperazine derivative flupenthixol) or increased it (the diphenylpiperazine derivative flunarizine or the chemically unrelated compounds fenfluramine and SKF 525A). A close correlation was found between occupancy of the striatal [ 3 H]GBR 12783 binding site and the stimulant locomotor effect of the drug. A similar specific striatal binding of [ 3 H]GBR 12783 was evidenced in both NMRI and CD1 strains. It was concluded that [ 3 H]GBR 12783 administered in vivo provides a measure of the density of Dopamine Uptake sites in mouse striatum.
Brian Dean - One of the best experts on this subject based on the ideXlab platform.
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Dopamine Uptake by platelets is selective, temperature dependent and not influenced by the Dopamine-D1 or Dopamine-D2 receptor
Life Sciences, 2002Co-Authors: Brian Dean, David L. CopolovAbstract:Abstract The human platelet, which takes up and releases Dopamine, has been proposed as a peripheral model for the study of Dopaminergic neurons in the central nervous system (CNS). In addition, the platelet has been shown to possess membrane components with pharmacological properties similar to the Dopamine-D1 (DA-D1) and D2 and (DA-D2) receptor on Dopaminergic neurons. We have therefore studied the specificity of the platelet Uptake system for Dopamine and, as Dopamine Uptake comprises both internalised and membrane bound Dopamine, the contribution of the DA-D1 and DA-D2 receptor to the Uptake of Dopamine has been assessed. Significant Uptake of 3H-Dopamine by platelet rich plasma (PRP) occurred after 10 min incubation at 37°C, Uptake being maximal after 90 min. In contrast, at 4°C no Uptake of 3H-Dopamine occurred up to 60 mins incubation but at 20°C was approximately 8% of the 60 min Uptake at 37°C. The neurotransmitters serotonin and Dopamine inhibited Dopamine Uptake by platelets in a dose dependent manner. Uptake of Dopamine appeared to be via two systems, one of high affinity with low capacity and the other of lower affinity but high capacity. In contrast, noradrenaline, adrenaline, acetylcholine, gamma-aminobutyric acid and histamine (10uM) had no effect on Dopamine Uptake by platelets. The DA-D1 receptor antagonist SCH 23390 (10um) and the DA-D2 receptor antagonists (10uM) spiperone, domperidone and (+)-butaclamol did not significantly affect Dopamine Uptake by platelets. In addition, ouabain and desipramine (100uM) inhibited Dopamine Uptake by 21% and 24% respectively whilst reserpine and imipramine (100uM) increased Uptake by 14% and 15%. We therefore conclude that platelets take up Dopamine via a selective, temperature dependent mechanism. Our data also suggest that Dopamine Uptake by platelets does not involve the DA-D1 or DA-D2 receptor.
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Typical and atypical neuroleptic drugs decrease platelet 3H-Dopamine Uptake in the rat
Psychiatry research, 1996Co-Authors: Suresh Sundram, Brian Dean, David L. CopolovAbstract:Reports of opposing changes in platelet 3H-Dopamine Uptake in neuroleptic-free versus neuroleptic-treated schizophrenic subjects have suggested an effect of neuroleptic treatment on this measure. We examined platelet 3H-Dopamine Uptake in rats treated with haloperidol or clozapine to determine if such treatment did affect platelet 3H-Dopamine Uptake. Neuroleptic drug treatment reduced platelet 3H-Dopamine Uptake in a dose- and time-dependent manner. After up to 4 weeks of treatment, these effects were reversed by the discontinuation of neuroleptic drug treatment. These data suggest that the effect of neuroleptic treatment in studies of platelet 3H-Dopamine Uptake could account for the variable findings in schizophrenia.
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Platelet [3H]Dopamine Uptake is differentially affected by neuroleptic drug treatment in schizophrenia and schizophreniform disorder
Progress in Neuro-Psychopharmacology and Biological Psychiatry, 1996Co-Authors: Brian Dean, Suresh Sundram, Christine Hill, David L. CopolovAbstract:Abstract 1. 1. The Uptake of [ 3 H]Dopamine was measured using platelet-rich plasma (PRP) from neurolepticfree subjects and again, in some cases, after the subject had been treated with neuroleptic drugs. 2. 2. There were no differences in [ 3 H]Dopamine Uptake by PRP in subjects who were or were not mentally ill. 3. 3. After treatment with neuroleptic drugs the Km for platelet [ 3 H]Dopamine Uptake had increased in 76% of subjects with schizophrenia and 87% of subjects with Schizophreniform disorder. Similarly, the Vmax for platelet [ 3 H]Dopamine Uptake had increased in 81% of the subjects with schizophrenia and 86% of the subjects with Schizophreniform disorder. 4. 4. By contrast, the Km for platelet [ 3 H]Dopamine Uptake had decreased in 94% of subjects who had a psychoses associated with an illness other than schizophrenia or schizophreniform disorder whilst the Vmax for platelet [ 3 H]Dopamine Uptake also decreased by 94% in these subjects. 5. 5. In subjects with psychoses, platelet [ 3 H]Dopamine Uptake is differentially altered during neuroleptic drug treatment depending on diagnosis.
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The development of a method to measure [3H] Dopamine Uptake by washed platelets provides no evidence for circulating inhibitors of platelet Dopamine Uptake in schizophrenia
Biological psychiatry, 1994Co-Authors: Suresh Sundram, Brian Dean, David L. CopolovAbstract:Altered [3H] Dopamine Uptake by platelet-rich plasma (PRP) has been reported in some subjects with schizophrenia (Rotman et al 1980; Dean et al 1990). As platelet Dopamine Uptake was measured using PRP, it was not possible to determine if the changes in schizophrenia were intrinsic to the platelet or due to plasma factors. Furthermore, the constraints of plasma as a medium for platelet suspension has hindered the study of the physiological requirements of platelet Dopamine Uptake. A method is now reported that allows platelets to be suspended in a controlled medium while preserving the Dopamine Uptake mechanism of the platelet. Dopamine Uptake by platelets in a controlled medium was dependent on temperature, energy, sodium, and chloride. Furthermore, plasma from subjects with schizophrenia and schizophreniform disorder did not significantly alter [3H] Dopamine Uptake by platelets compared to the effect of plasma from control subjects. Hence, these data provide no evidence for a circulating inhibitor of platelet [3H] Dopamine Uptake in plasma from subjects with schizophrenia.
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Dopamine Uptake by platelets from subjects with schizophrenia: a correlation with the delusional state of the patient.
Psychiatry research, 1992Co-Authors: Brian Dean, David L. Copolov, Jayashri Kulkarni, Preethi Shrikanthan, Valcy Malone, Christine HillAbstract:Abstract The Uptake of 3 H-Dopamine by platelets from patients with a number of psychiatric disorders has been compared with that by platelets from normal volunteers. Overall, 3 H-Dopamine Uptake by platelet-rich plasma (PRP) from 25 schizophrenic subjects did not differ from 3 H-Dopamine Uptake by PRP from 22 nonschizophrenic patients and 61 normal volunteers. In the schizophrenic group, however, there was an increased spread of results with seven values falling outside the range of results observed in the control group. Furthermore, of the patients rated, only for the schizophrenic patients was there an inverse correlation between 3 H-Dopamine Uptake by platelets and the rating for delusions on the Scale for the Assessment of Positive Symptoms. Thus, 3 H-Dopamine Uptake by platelets seems, in some way, to be linked to the delusional state of the patient. Further study of 3 H-Dopamine Uptake by platelets is warranted in a larger and more diverse group of patients to determine the significance of altered Dopamine Uptake by platelets from some schizophrenic subjects and the correlation between platelet 3 H-Dopamine Uptake and the delusional state of these subjects.
Annette E. Fleckenstein - One of the best experts on this subject based on the ideXlab platform.
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methamphetamine rapidly decreases vesicular Dopamine Uptake
Journal of Neurochemistry, 2008Co-Authors: Jeffrey M Brown, Glen R. Hanson, Annette E. FleckensteinAbstract:Vesicular sequestration is important in the regulation of cytoplasmic concentrations of monoamines such as Dopamine. Moreover, recent evidence suggests that increases in cytoplasmic Dopamine levels, perhaps attributable to changes in vesicular monoamine transporter function, contribute to methamphetamine-induced Dopaminergic deficits. Hence, we examined whether striatal vesicular Uptake is altered following methamphetamine treatment. Multiple administrations of methamphetamine rapidly (within 1 h) decreased vesicular Dopamine Uptake and dihydrotetrabenazine binding, an effect that (a) persisted at least 24 h, (b) was associated with Dopamine and not serotonin neurons, and (c) was unrelated to residual drug introduced by the original methamphetamine treatment. These data suggest that methamphetamine rapidly decreases vesicular monoamine transporter function in Dopaminergic neurons, a phenomenon that may be associated with the long-term damage caused by this stimulant.
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Methamphetamine rapidly decreases mouse vesicular Dopamine Uptake: role of hyperthermia and Dopamine D2 receptors.
European journal of pharmacology, 2003Co-Authors: Yvette V. Ugarte, Glen R. Hanson, Kristi S. Rau, Evan L. Riddle, Annette E. FleckensteinAbstract:Multiple high-dose administrations of the Dopamine-releasing agent, methamphetamine, rapidly and persistently decrease vesicular Dopamine Uptake in purified vesicles prepared from striata of treated rats. Because important differences in the neurotoxic effects of stimulants have been documented in rats and mice, the purpose of this study was to determine if methamphetamine-induced effects in rats occur in mice and to elucidate mechanisms underlying these effects. Results reveal methamphetamine treatment rapidly decreased mouse striatal vesicular Dopamine Uptake; a phenomenon associated with a subcellular redistribution of vesicular monoamine transporter-2 (VMAT-2) immunoreactivity. Both methamphetamine-induced hyperthermia and Dopamine D2 receptor activation contributed to the stimulant-induced deficits in vesicular Dopamine Uptake. Unlike methamphetamine, the Dopamine reUptake inhibitors, methylphenidate and cocaine, rapidly increased vesicular Dopamine Uptake. The implications of these phenomena are discussed.
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Phencyclidine increases vesicular Dopamine Uptake
European Journal of Pharmacology, 2002Co-Authors: Michael J. Crosby, Jarom E. Hanson, Annette E. Fleckenstein, Glen R. HansonAbstract:Phencyclidine (PCP) rapidly (within 1 h) increased vesicular Dopamine Uptake and binding of the vesicular monoamine transporter-2 (VMAT-2) ligand, dihydrotetrabenazine. Uptake returned to basal values 3 h in the striatum after a high-dose administration of this drug (15 mg/kg i.p.). In contrast, a similar pretreatment with another non-competitive NMDA receptor antagonist, dizocilpine;([5R,10S]-[+]-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine; MK-801; 1 mg/kg, i.p.), was without effect on vesicular Dopamine Uptake. Pretreatment with the Dopamine D2 receptor antagonist, eticlopride, blocked the increase in vesicular Dopamine Uptake caused by PCP administration. These data demonstrate a heretofore unreported mechanism that may contribute to the ability of PCP to influence Dopamine neuronal function and exert its pharmacological effects.
Glen R. Hanson - One of the best experts on this subject based on the ideXlab platform.
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methamphetamine rapidly decreases vesicular Dopamine Uptake
Journal of Neurochemistry, 2008Co-Authors: Jeffrey M Brown, Glen R. Hanson, Annette E. FleckensteinAbstract:Vesicular sequestration is important in the regulation of cytoplasmic concentrations of monoamines such as Dopamine. Moreover, recent evidence suggests that increases in cytoplasmic Dopamine levels, perhaps attributable to changes in vesicular monoamine transporter function, contribute to methamphetamine-induced Dopaminergic deficits. Hence, we examined whether striatal vesicular Uptake is altered following methamphetamine treatment. Multiple administrations of methamphetamine rapidly (within 1 h) decreased vesicular Dopamine Uptake and dihydrotetrabenazine binding, an effect that (a) persisted at least 24 h, (b) was associated with Dopamine and not serotonin neurons, and (c) was unrelated to residual drug introduced by the original methamphetamine treatment. These data suggest that methamphetamine rapidly decreases vesicular monoamine transporter function in Dopaminergic neurons, a phenomenon that may be associated with the long-term damage caused by this stimulant.
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Methamphetamine rapidly decreases mouse vesicular Dopamine Uptake: role of hyperthermia and Dopamine D2 receptors.
European journal of pharmacology, 2003Co-Authors: Yvette V. Ugarte, Glen R. Hanson, Kristi S. Rau, Evan L. Riddle, Annette E. FleckensteinAbstract:Multiple high-dose administrations of the Dopamine-releasing agent, methamphetamine, rapidly and persistently decrease vesicular Dopamine Uptake in purified vesicles prepared from striata of treated rats. Because important differences in the neurotoxic effects of stimulants have been documented in rats and mice, the purpose of this study was to determine if methamphetamine-induced effects in rats occur in mice and to elucidate mechanisms underlying these effects. Results reveal methamphetamine treatment rapidly decreased mouse striatal vesicular Dopamine Uptake; a phenomenon associated with a subcellular redistribution of vesicular monoamine transporter-2 (VMAT-2) immunoreactivity. Both methamphetamine-induced hyperthermia and Dopamine D2 receptor activation contributed to the stimulant-induced deficits in vesicular Dopamine Uptake. Unlike methamphetamine, the Dopamine reUptake inhibitors, methylphenidate and cocaine, rapidly increased vesicular Dopamine Uptake. The implications of these phenomena are discussed.
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Phencyclidine increases vesicular Dopamine Uptake
European Journal of Pharmacology, 2002Co-Authors: Michael J. Crosby, Jarom E. Hanson, Annette E. Fleckenstein, Glen R. HansonAbstract:Phencyclidine (PCP) rapidly (within 1 h) increased vesicular Dopamine Uptake and binding of the vesicular monoamine transporter-2 (VMAT-2) ligand, dihydrotetrabenazine. Uptake returned to basal values 3 h in the striatum after a high-dose administration of this drug (15 mg/kg i.p.). In contrast, a similar pretreatment with another non-competitive NMDA receptor antagonist, dizocilpine;([5R,10S]-[+]-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine; MK-801; 1 mg/kg, i.p.), was without effect on vesicular Dopamine Uptake. Pretreatment with the Dopamine D2 receptor antagonist, eticlopride, blocked the increase in vesicular Dopamine Uptake caused by PCP administration. These data demonstrate a heretofore unreported mechanism that may contribute to the ability of PCP to influence Dopamine neuronal function and exert its pharmacological effects.