In Vivo and in Vitro Assessment of Dopamine Uptake and Release

Ge, Mickelson; Garris, PA; Bunin, Melissa A.; Rm, Wightman

doi:10.1016/s1054-3589(08)60716-4

Cited by 6 publications

(6 citation statements)

References 7 publications

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“…For currents Ͼ300 A, no additional increase in maximal 5-HT concentration was observed. This behavior is identical to that obtained for dopamine release in vivo during stimulation of the medial forebrain bundle (Kuhr et al, 1984; but differs from that for dopamine release in slices (Mickelson et al, 1998). All subsequent measurements were made by using a current amplitude in the plateau region (350 A) to ensure maximal release.…”

Section: Effect Of Stimulation Amplitude On Evoked 5-ht Releasesupporting

confidence: 63%

Quantitative Evaluation of 5-Hydroxytryptamine (Serotonin) Neuronal Release and Uptake: An Investigation of Extrasynaptic Transmission

1998

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Whether neurotransmitters are restricted to the synaptic cleft (participating only in hard-wired neurotransmission) or diffuse to remote receptor sites (participating in what has been termed volume or paracrine transmission) depends on a number of factors. These include (1) the location of release sites with respect to the receptors, (2) the number of molecules released, (3) the diffusional rate away from the release site, determined by both the geometry near the release site as well as binding interactions, and (4) the removal of transmitter by the relevant transporter. Fast-scan cyclic voltammetry allows for the detection of extrasynaptic concentrations of many biogenic amines, permitting direct access to many of these parameters. In this study the hypothesis that 5-hydroxytryptamine (5-HT) transmission is primarily extrasynaptic in the substantia nigra reticulata, a terminal region with identified synaptic contacts, and the dorsal raphe nucleus, a somatodendritic region with rare synaptic incidence, was tested in brain slices prepared from the rat. Using carbon fiber microelectrodes, we found the concentration of 5-HT released per stimulus pulse in both regions to be identical when elicited by single pulse stimulations or trains at high frequency. 5-HT efflux elicited by a single stimulus pulse was unaffected by uptake inhibition or receptor antagonism. Thus, synaptic efflux is not restricted by binding to intrasynaptic receptors or transporters. The number of 5-HT molecules released per terminal was estimated in the substantia nigra reticulata and was considerably less than the number of 5-HT transporter and receptor sites, reinforcing the hypothesis that these sites are extrasynaptic. Furthermore, the detected extrasynaptic concentrations closely match the affinity for the predominant 5-HT receptor in each region. Although they do not disprove the existence of classical synaptic transmission, our results support the existence of paracrine neurotransmission in both serotonergic regions.

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Section: Effect Of Stimulation Amplitude On Evoked 5-ht Releasesupporting

confidence: 63%

Quantitative Evaluation of 5-Hydroxytryptamine (Serotonin) Neuronal Release and Uptake: An Investigation of Extrasynaptic Transmission

1998

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“…Different regions of the brain exhibit different V max values for DA. However, K m and V max are fairly consistent across FSCV in both slice (Jones et al, 1995a, Jones et al, 1995b and anesthetized preparations , Cass and Gerhardt, 1995, Mickelson et al, 1998, Wu et al, 2001, Addy et al, 2010 and are consistent with values obtained using [ 3 H] DA radiolabeling techniques (described below). For example, K m is usually reported in the range of 0.1µM to 0.3µM in the caudate-putamen and nucleus accumbens, with a mean of 0.2µM.…”

Section: Fast-scan Cyclic Voltammetrysupporting

confidence: 78%

Advances in studying phasic dopamine signaling in brain reward mechanisms

et al. 2013

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The last sixty years of research have provided extraordinary advances of our knowledge of the reward system. Since its initial discovery as a neurotransmitter by Carlsson and colleagues (Carlsson et al., 1957), dopamine (DA) has emerged as an important mediator of reward processing. As a result, a number of electrochemical techniques have been developed to directly measure DA levels in the brain using various preparations. Many of these techniques and preparations differ in the types of questions that they can address. Together, these techniques have begun to elucidate the complex roles of tonic and phasic DA signaling in reward processing and in addiction. In this review, we will first provide a guide for the most commonly used electrochemical methods for DA detection and describe their utility in furthering our knowledge about DA's role in reward and addiction. Second, we will review the value of common in vitro and in vivo preparations and describe their ability to address different types of questions. Last, we will review recent data that has provided new insight of the mechanisms of in vivo phasic DA signaling and its role in reward processing and reward-mediated behavior.

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“…Although the concentration of DA required to activate 5-HT receptors in this study is quite high for the classical DA-receptor activation, synaptic concentrations of DA during quantal release may reach such high concentrations (for review, see Sulzer and Pothos, 2000). In addition, synaptically evoked DA release in rat caudate slices has been found to be in the range of 1-2 M (Mickelson et al, 1998), suggesting that DA concentrations at or near release sites may be much higher than these values. In line with these findings, in experiments conducted in mammalian cell lines at 37°C, DA at low micromolar concentrations of DA displaced the binding of 8-OH-DPAT and inhibited the forskolin-induced cAMP accumulation, suggesting that direct activation of 5-HT 1A receptors by DA may have functional roles in 5-HT receptor-mediated responses.…”

Section: Discussionmentioning

confidence: 71%

Direct activation by dopamine of recombinant human 5‐HT_1A receptors: Comparison with human 5‐HT_2C and 5‐HT₃ receptors

Öz

Zhang

Rotondo

et al. 2003

Synapse

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The effects of dopamine (DA) on the function of human 5-HT1A receptors expressed in Xenopus oocytes and CHO-K1 cells were investigated. In addition, the effect of DA on the activation of three different types of human 5-HT receptors (5-HT1A, 5-HT2C, and 5-HT3) were studied comparatively in Xenopus oocyte expression system. Application of 5-HT or DA in oocytes coexpressing 5-HT1A receptors and G-protein-activated inwardly rectifying potassium channels (GIRK1) induced inward currents with respective EC50 values of 4.2 nM and 11.2 microM. Maximal responses induced by DA were 85 +/- 4% of maximal 5-HT currents and DA responses were blocked by the specific 5-HT1A antagonist, WAY-100635 (50 nM). In CHO-K1 cells expressing 5-HT1A receptors, 5-HT and DA inhibited the specific binding of selective antagonist [3H]-8-OH-DPAT with IC50 values of 10.2 nM and 1.4 microM, and both 5-HT and DA inhibited the forskolin-induced accumulation of cAMP. In oocytes expressing 5-HT2C receptors, 5-HT and DA induced inward currents with respective EC50 values of 6.2 nM and 67.7 microM. Magnitudes of maximal DA induced currents were 42 +/- 3% of maximal 5-HT responses and blocked by the 5-HT2 antagonist, piperazine (1 microM). In oocytes expressing 5-HT3 receptors, 5-HT and DA induced fast inward currents with respective EC50 values of 2.1 microM and 266.3 microM. Maximal DA induced currents were 37 +/- 3% of maximal 5-HT responses and blocked the specific 5-HT3 antagonist LY-278584 (0.1 microM). Comparison of the potencies and efficacies of 5-HT and DA indicated that the relative potency of DA increased in the order of 5-HT3 > 5-HT1A > 5-HT2C, and relative efficacy increased in the order of 5-HT1A > 5-HT2C > 5-HT3. These results suggest that although DA activates different subtypes of human 5-HT receptors directly, the potency and efficacy of the binding site varies significantly among different receptors.

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In Vivo and in Vitro Assessment of Dopamine Uptake and Release

Cited by 6 publications

References 7 publications

Quantitative Evaluation of 5-Hydroxytryptamine (Serotonin) Neuronal Release and Uptake: An Investigation of Extrasynaptic Transmission

Quantitative Evaluation of 5-Hydroxytryptamine (Serotonin) Neuronal Release and Uptake: An Investigation of Extrasynaptic Transmission

Advances in studying phasic dopamine signaling in brain reward mechanisms

Direct activation by dopamine of recombinant human 5‐HT_1A receptors: Comparison with human 5‐HT_2C and 5‐HT₃ receptors

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In Vivo and in Vitro Assessment of Dopamine Uptake and Release

Cited by 6 publications

References 7 publications

Quantitative Evaluation of 5-Hydroxytryptamine (Serotonin) Neuronal Release and Uptake: An Investigation of Extrasynaptic Transmission

Quantitative Evaluation of 5-Hydroxytryptamine (Serotonin) Neuronal Release and Uptake: An Investigation of Extrasynaptic Transmission

Advances in studying phasic dopamine signaling in brain reward mechanisms

Direct activation by dopamine of recombinant human 5‐HT1A receptors: Comparison with human 5‐HT2C and 5‐HT3 receptors

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Direct activation by dopamine of recombinant human 5‐HT_1A receptors: Comparison with human 5‐HT_2C and 5‐HT₃ receptors