Sodium-independent binding of [3H]cocaine in mouse striatum is serotonin related

Reith, Maarten E. A.; Meisler, Bernard E.; Sershen, Henry; Lajtha, Ábel

doi:10.1016/0006-8993(85)91363-0

Cited by 36 publications

(12 citation statements)

References 8 publications

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“…Among these, one may consider the involvement of phenylethylamine, whose formation is increased after amphetamine , stimulation of sigma receptors by GBR 12909 (Ross, 1991), serotonin and noradrenaline reuptake inhibition by cocaine (Reith et al, 1986), and noradrenaline reuptake inhibition by nomifensine (Schacht et al, 1982). Dopamine uptake into noradrenergic terminals constitutes a prominent mechanism for DA removal in the frontal cortex .…”

Section: Discussionmentioning

confidence: 99%

Regional effects of amphetamine, cocaine, nomifensine and GBR 12909 on the dynamics of dopamine release and metabolism in the rat brain

Karoum

Chrapusta

Brinjak

et al. 1994

British J Pharmacology

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1 The effects of single-dose regimens of amphetamine, cocaine, nomifensine and GBR 12909 on the dynamics of dopamine (DA) release and metabolism were evaluated in the frontal cortex, hypothalamus, nucleus accumbens and striatum. The regimens selected are known to produce substantial behavioural effects. 2 3-Methoxytyramine (3MT) and 3,4-dihydroxyphenylacetic acid (DOPAC) rates of formation were used to assess DA metabolism by catechol-O-methyltransferase and monoamine oxidase respectively. The rate of formation of 3MT was used as an index of synaptic DA. The ratio and sum, respectively, of 3MT and DOPAC rates of formation were used to assess DA reuptake inhibition and turnover. 3 The effects of amphetamine on 3MT production and DOPAC steady-state levels were similar in all regions, suggesting similar pharmacodynamic actions. Amphetamine increased 3MT formation and steady-state levels, and reduced DOPAC steady-state levels. DOPAC formation was significantly reduced only in the nucleus accumbens and striatum. Total DA turnover remained unchanged except in the nucleus accumbens. Apparently, the amphetamine-induced increase in DA release occurred at the expense of intraneuronal DA metabolism and did not require stimulation of synthesis. 4 Nomifensine elevated 3MT formation in all regions. A similar effect was produced by cocaine except in the nucleus accumbens. GBR 12909 elevated 3MT production only in the hypothalamus, the striatum and the nucleus accumbens. 5 Cocaine selectively reduced DOPAC formation in the frontal cortex. Nomifensine increased and reduced, respectively, DOPAC formation in striatum and hypothalamus. GBR 12909 elevated DOPAC formation in all regions except the cortex, where pargyline did not reduce DOPAC levels in GBR 12909-treated rats. 6 Ratios and sum of 3MT and DOPAC rates of formation also exhibited wide regional variations for each drug. In contrast to the other drugs, the ratio was not increased after GBR 12909. Apparently, the DA uptake properties of this drug are poorly related to its in vivo effects on the ratio of 3MT production to that of DOPAC, which should increase when DA reuptake is inhibited. 7 Total DA turnover was increased by GBR 12909 in the hypothalamus, nucleus accumbens and striatum, while cocaine and nomifensine increased it only in the nucleus accumbens and striatum respectively. 8 It is concluded that: (a) 3MT and DOPAC rates of formation provide better indices of DA release and metabolism than do their steady-state concentrations. (b) Some effects of DA uptake blockers on DA transmission, especially those of nomifensine and cocaine, may be attributed to increased DA release. (c) Patterns of regional effects of psychostimulants on the dynamics of DA release and metabolism may be better biochemical correlates of stimulant-induced behaviours than would changes in any single region.

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Section: Discussionmentioning

confidence: 99%

Regional effects of amphetamine, cocaine, nomifensine and GBR 12909 on the dynamics of dopamine release and metabolism in the rat brain

Karoum

Chrapusta

Brinjak

et al. 1994

British J Pharmacology

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“…The binding of various other dopamine uptake ligands is stimulated by Na+, generally by an increase in affinity (Table 2) (Javitch et al, 1984;Janowsky et al, 1986;Bonnet et al, 1988;Zimanyi et al, 1989) (note that this effect has been observed under various conditions of membrane preparation and assay buffer). The reported enhancement of the B,,, of [3H]cocaine binding by Na+ (Kennedy and Hanbauer, 1983) may be related to complexities in [3H]cocaine binding such as heterogeneity (Reith et al, 1985;Calligaro and Eldefrawi, 1988;Madras et al, 1989b) and extremely rapid dissociation rate (Reith et al, 1986b). Taken together, the data on stimulation by Na+ allow the conclusion that the postulated "cation" site at which Na+ regulates the affinity of [3H]GBR 12783 binding (Bonnet et al, 1988) is also part of the binding domain of other ligands, including cocaine-related compounds.…”

Section: And Equilibrium Binding Experiments (Time Scale Of Hours) (Pmentioning

confidence: 99%

Cationic and Anionic Requirements for the Binding of 2β‐Carbomethoxy‐3β‐(4‐Fluorophenyl)[³H]tropane to the Dopamine Uptake Carrier

Reith

Coffey

1993

Journal of Neurochemistry

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The present study reports the ion dependency of 2 beta-carbomethoxy-3 beta-(4-fluorophenyl)[3H]tropane ([3H]CFT) binding to the dopamine transporter in the rat striatum. The results indicate that [3H]CFT binding to synaptosomal P2 membranes requires low concentrations of Na+ (peak binding between 20 and 50 mM Na+), is stimulated by phosphate anion or I-, but is unaffected or only slightly affected by F-, Cl-, Br-, NO3-, or SO(4)2-. Concentrations of Na+ of > 50 mM become inhibitory except in the presence of I-, which shifts peak binding levels toward higher Na+ concentrations and also elevates the peak binding level. K+ strongly decreased [3H]CFT binding with a shallow inhibition curve, and Na+ could not overcome this effect. Saturation analysis of [3H]CFT binding revealed a single binding site changing its affinity for CFT depending on the concentration of sodium phosphate buffer (6, 10, 30, 50, 130, or 200 mM; 1 mM plus 49 mM NaCl versus 10 mM plus 40 mM NaCl; or 1 mM plus 129 mM NaI versus 10 mM plus 120 mM NaI). No differences were observed in the density of CFT binding sites between any of the conditions examined.

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“…Indeed, in in vivo binding studies, a greater fraction of total binding is specific when [3H]WIN 35,065-2 and [3H]WIN 35,428 are used than when [3H]cocaine is used (Scheffel et al, 1989). Finally, our results suggest that [3HJWIN 35,065-2 does not interact with the serotonin transporter in striatum as cocaine does (Reith et al, 1985). This finding may be due in part to the observation that cocaine has a higher affinity for the serotonin transporter than for the dopamine transporter, whereas WIN 35,065-2 exhibits equal affinities for both (Reith et al, 1986;Ritz et al, 1987).…”

Section: Discussionmentioning

confidence: 64%

“…[3H]WIN 35,065-2 is an important ligand to use for studying these sites, because it does not have a higher affinity at the serotonin or norepinephrine transporter, relative to the dopamine transporter, as do [3H]cocaine and some other analogs such as WIN 35,428 and WIN 35,981 (Ritz et al, 1987). [3H]Cocaine binding sites that appear to be associated with the serotonin transporter have been identified in cortical tissues by other investigators (Reith et al, 1980(Reith et al, , 1983(Reith et al, , 1985. Specifically, these reports suggest that lesions of serotonergic neurons may decrease the number of these cocaine binding sites in mouse cortex.…”

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confidence: 88%

[³H]WIN 35,065–2: A Ligand for Cocaine Receptors in Striatum

Ritz¹,

Boja²,

Grigoriadis³

et al. 1990

Journal of Neurochemistry

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[3H]WIN 35,065-2 binding to striatal membranes was characterized, primarily by centrifugation assay. Like [3H]cocaine, [3H]WIN 35,065-2 binds to both high- and low-affinity sites. [3H]WIN 35,065-2, however, exhibits consistently higher affinities than [3H]cocaine. Saturation experiments indicate a low-affinity binding site with an apparent KD of approximately 160 nM and a Bmax of 135 fmol/mg of tissue. A high-affinity site has also been identified with an apparent KD of 5.6 nM and a Bmax of 5.2 fmol/mg of tissue. The specific-to-nonspecific binding ratios with [3H]WIN 35,065-2 were higher than with [3H]cocaine in both centrifugation and filtration assays. Pharmacological characterization suggests that [3H]WIN 35,065-2 binds to the dopamine transporter. Mazindol, GBR 12909, nomifensine, and (-)-cocaine are potent inhibitors of [3H]WIN 35,065-2 binding. In contrast, the norepinephrine transporter ligand desipramine is a weak inhibitor, and the serotonin transporter ligand citalopram does not inhibit binding. The effect of sodium on binding was examined under conditions in which (a) the low-affinity site was primarily (87%) occupied and (b) approximately 50% of both sites were occupied. The results indicate that both sites are sodium dependent. Injection of 6-hydroxydopamine into the striatum results in a significant loss of both high- and low-affinity sites, a finding suggesting that both sites are on dopaminergic nerve terminals. Taken together, these data are consistent with the presence of multiple cocaine binding sites associated with the dopamine transporter.

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Sodium-independent binding of [3H]cocaine in mouse striatum is serotonin related

Cited by 36 publications

References 8 publications

Regional effects of amphetamine, cocaine, nomifensine and GBR 12909 on the dynamics of dopamine release and metabolism in the rat brain

Regional effects of amphetamine, cocaine, nomifensine and GBR 12909 on the dynamics of dopamine release and metabolism in the rat brain

Cationic and Anionic Requirements for the Binding of 2β‐Carbomethoxy‐3β‐(4‐Fluorophenyl)[³H]tropane to the Dopamine Uptake Carrier

[³H]WIN 35,065–2: A Ligand for Cocaine Receptors in Striatum

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Sodium-independent binding of [3H]cocaine in mouse striatum is serotonin related

Cited by 36 publications

References 8 publications

Regional effects of amphetamine, cocaine, nomifensine and GBR 12909 on the dynamics of dopamine release and metabolism in the rat brain

Regional effects of amphetamine, cocaine, nomifensine and GBR 12909 on the dynamics of dopamine release and metabolism in the rat brain

Cationic and Anionic Requirements for the Binding of 2β‐Carbomethoxy‐3β‐(4‐Fluorophenyl)[3H]tropane to the Dopamine Uptake Carrier

[3H]WIN 35,065–2: A Ligand for Cocaine Receptors in Striatum

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Cationic and Anionic Requirements for the Binding of 2β‐Carbomethoxy‐3β‐(4‐Fluorophenyl)[³H]tropane to the Dopamine Uptake Carrier

[³H]WIN 35,065–2: A Ligand for Cocaine Receptors in Striatum