Sodium dependent [3H]cocaine binding associated with dopamine uptake sites in the rat striatum and human putamen decrease after dopaminergic denervation and in Parkinsons disease

Schoemaker, Hans E.; Pimoule, C.; Arbilla, S.; Scatton, B.; Javoy‐Agid, F.; Langer, Salomón Z.

doi:10.1007/bf00501873

Cited by 167 publications

(123 citation statements)

References 32 publications

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“…Two binding sites have been reported in rat caudate putamen (Schoemaker et al 1985;Izenwasser et al 1993) and human caudate (Little et al 1993) and putamen (Schoemaker et al 1985;Staley et al 1994). In monkey brain, the binding of both [ 3 H]cocaine and the more potent cocaine analog [ 3 H]WIN35,428, fit a two-site binding model better than a one-site model (Madras et al 1989a(Madras et al , 1989b.…”

Section: Discussionmentioning

confidence: 98%

Relationships among dopamine transporter affinities and cocaine-like discriminative-stimulus effects

Katz¹,

Izenwasser²,

Terry

2000

Psychopharmacology

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Rationale: The discriminative-stimulus effects of cocaine have been reported to be mediated by indirect agonist actions initiated by the blockade of dopamine uptake, and the potencies of drugs that have discriminativestimulus effects like cocaine are directly related to their dopamine transporter binding affinities. The binding to the dopamine transporter by cocaine and many of its analogs has been reported to fit better using a two-site model than a one-site model. Objectives: The present study examined the relationship among binding affinities of dopamine uptake inhibitors at these two sites and their potencies to produce discriminative-stimulus effects. Methods: The inhibition constants (K i values) were derived for unlabeled dopamine uptake inhibitors for displacement of [ 3 H]WIN 35,428 from rat caudate putamen membranes. These K i values were related to the ED 50 values obtained in rats trained to discriminate 10 mg/kg cocaine from saline injections under a fixed-ratio 20 schedule of food reinforcement. Results: Among the dopamine uptake inhibitors studied, the binding data for eight compounds (WIN 35,428, nomifensine, WIN 35,981, WIN 35,065-2, methylphenidate, cocaine, cocaethylene, and bupropion) were better fit by a two-site model than a one-site model. The data for the remaining eleven compounds (RTI-31, RTI-55, RTI-121, RTI-32, LU19-005, BTCP, GBR12909, GBR12935, mazindol, LU17-133, and EXP561) were better fit by a one-site model. Of the drugs that were fit best by a two-site model, there was a higher correlation among the K i values for the high-affinity site and the ED 50 values (R 2 =0.655; P=0.015) than there was for the low-affinity site (R 2 =0.543; P=0.037). Of the remaining drugs, there was a high correlation among the K i values and the ED 50 values for the discriminative-stimulus effects (R 2 =0.523; P=0.012). Conclusions: These data suggest that the discriminative-stimulus effects of cocaine are more closely related to actions mediated by high-affinity binding to the dopamine transporter than they are to actions mediated by the low-affinity site. The further assessment of the respective contributions of high-and lowaffinity binding to the behavioral effects of cocaine will be greatly enhanced with the development of pharmacological tools that have a high degree of selectivity for one of these components.

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Section: Discussionmentioning

confidence: 98%

Relationships among dopamine transporter affinities and cocaine-like discriminative-stimulus effects

Katz¹,

Izenwasser²,

Terry

2000

Psychopharmacology

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“…Cocaine metabolites, ecgonine derivatives, have been shown not to generalize to cocaine in previous operant behavioral studies (34).…”

Section: Discussionmentioning

confidence: 98%

“…Schoemaker et al (1985) indicates that serotonin (IC50=24.5 ~M) may be slightly less potent than dopamlne (IC50=I0.6 ~M) in inhibiting 3H-cocaine binding to striatal membranes. Our data indicates that serotonin (KD=2.7 ~M) may be slightly more potent in inhibiting 3H-mazindol binding in striatum than dopamine (KD=8.7 ~M).…”

Section: Discussionmentioning

confidence: 99%

Cocaine inhibition of ligand binding at dopamine, norepinephrine and serotonin transporters: A structure-activity study

Ritz¹,

Cone²,

Kuhar³

1990

Life Sciences

447

270

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SummaryStructure-activlty relationships for cocaine and analog binding at the depamine, norepinephrine and serotonin transporters were determined.Cocaine inhibition of llgand binding to each of these sites has a stereospecific requirement for the levorotatory isomer. Binding potencies of cocaine derivatives involving N-substltution, C2 and C3 substituent modifications, however, revealed differences in structure-activity relationships for cocaine binding at the transporters.Removal of the N-methyl groups produced little change in binding potency at the dopamlne transporter site hut produced increases in binding potency at norepinephrlne and serotonin transporter sites.Changes in structure at the C2 substituent produced changes in binding potency at the dopamlne transporter which were generally similar in direction, but not necessarily in magnitude at the noreplnephrine and serotonin transporters.Modifications to the C3 substituent, especially substitution of a hydroxyl moiety, produce changes in affinity at norepinephrine and serotonin transporters which are much larger than those observed at dopamine transporters.In general, our results indicate that unique structural requirements exist for each transporter site, but that cocaine binding at norepinephrine and dopamine transporters can be described by more similar structure-actlvity relationships than those found for the serotonin transporter.Reguirements for cocaine binding to the dopamine transporter, which we have previously shown to be associated with the reinforcing effects of cocaine, include levorotatory sterospeclficlty, the benzene ring at C3, at least some portions of the tropane ring, and the presence of the C2 methyl ester group in the ~ conformation.

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“…Cocaine binds to specific receptors that block presynaptic dopamine reuptake (Kennedy & Hanbauer, 1983;Schoemaker et al, 1985), whereas amphetamine results in the release of dopamine and direct postsynaptic activation (Cooper, Bloom, & Roth, 1982). Moreover, the contingent administration of amphetamine but not cocaine into the nucleus accumbens has been shown to be reinforcing (Goeders & Smith, 1983).…”

Section: Discussionmentioning

confidence: 99%

Differential Effects of Pentobarbital and Cocaine on Punished and Nonpunished Responding

Dworkin¹,

Bimle²,

Miyauchi³

1989

J Exper Analysis Behavior

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Similar rates of punished and nonpunished responding, maintained with equated rates of reinforcement, were established in pairs of rats. One subject of each pair was exposed to a random-ratio schedule of food presentation. The interreinforcement intervals for this subject comprised the intervals of a randominterval schedule of reinforcement for the other (yoked) rat. The random-ratio schedule maintained rates of responding higher than those maintained by the same rate of reinforcement schedule according to the yoked random-interval contingency. A random-ratio schedule of electric foot shock added to the random-ratio schedule of food presentation suppressed rates of responding such that similar rates of responding were observed in rats of both groups. Pentobarbital (3.0 to 17.0 mg/kg) increased punished responding at doses that had little effect on or decreased nonpunished responding, whereas cocaine (5.6 to 30 mg/kg) increased nonpunished responding at doses that decreased or did not alter punished responding. Qualitatively different effects of pharmacological agents on punished and nonpunished responding can be obtained using procedures that generate similar rates and temporal patterns of punished and nonpunished responding. The effects of pentobarbital and cocaine on responding can be determined by factors other than simply the baseline rate of responding.

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Sodium dependent [3H]cocaine binding associated with dopamine uptake sites in the rat striatum and human putamen decrease after dopaminergic denervation and in Parkinsons disease

Cited by 167 publications

References 32 publications

Relationships among dopamine transporter affinities and cocaine-like discriminative-stimulus effects

Relationships among dopamine transporter affinities and cocaine-like discriminative-stimulus effects

Cocaine inhibition of ligand binding at dopamine, norepinephrine and serotonin transporters: A structure-activity study

Differential Effects of Pentobarbital and Cocaine on Punished and Nonpunished Responding

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