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Behavioral/Systems/Cognitive

Constitutive Activity of the Serotonin2C Receptor Inhibits In Vivo Dopamine Release in the Rat Striatum and Nucleus Accumbens

Philippe De Deurwaerdère, Sylvia Navailles, Kelly A Berg, William P. Clarke and Umberto Spampinato
Journal of Neuroscience 31 March 2004, 24 (13) 3235-3241; https://doi.org/10.1523/JNEUROSCI.0112-04.2004
Philippe De Deurwaerdère
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Sylvia Navailles
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Kelly A Berg
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William P. Clarke
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Umberto Spampinato
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    Figure 1.

    Pharmacological properties of SB 206553 and SB 242084 in CHO-1C7 cells. Cells, prelabeled with [3H]-AA and myo-[3H]inositol, were incubated with the indicated drugs for 25 min in the presence of LiCL (20 mm) and 0.1% fatty acid-free BSA. a–c, Concentration–response curves for SB 242084 and SB 206553 measuring IP accumulation [SB 206553 alone and in the presence of 100 nm SB 242084 (a)], AA release (b), or [γ35S]GTP binding (c). Basal IP accumulation, AA release, and [γ35S]GTP binding levels were as follows: 1544±167 dpm, 5378±789 dpm, and 72±13 pmol/mg protein, respectively. Data are expressed as the mean ± SEM of six (a, b) or four (c) independent experiments.

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    Figure 2.

    Dose–response effects of 5-HT2C receptor ligands on basal DA release in the striatum and the nucleus accumbens. The inverse agonist SB 206553 (a, b), the antagonist SB 242084 (c, d), and the agonist Ro-60–0175 (e, f) and their corresponding vehicle (v) were administered intraperitoneally (doses in milligrams per kilogram) as indicated by vertical arrows. Data represent mean ± SEM percentages of baseline in each sample (time courses) or averaged over 2.5 hr monitoring (Insets: doses in milligrams per kilogram indicated in histograms or below) (n = 4–6 animals/group). *p < 0.05, **p < 0.01, and ***p < 0.001 versus the vehicle group (Fisher's PLSD test).

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    Figure 3.

    Effect of central 5-HT2C receptor blockade on 5-HT2C receptor ligands mediated responses on DA release in vivo. Reversal by SB 242084 (1 mg/kg) of the DA effects elicited by 5 mg/kg SB 206553 (inverse agonist) (a, b) and 3 mg/kg Ro-60–0175 (agonist) (c, d) in the striatum and the nucleus accumbens. SB 242084 (SB242) was administered 30 min before SB 206553 (SB206) or Ro-60–0175 (Ro) as indicated by vertical arrows. Data represent mean ± SEM percentages of baseline in each sample (time courses) or averaged over 2 hr monitoring (insets) (n = 6–9 animals/group). *p < 0.05, **p < 0.01, and ***p < 0.001 versus the vehicle–vehicle (v/v) group and +p < 0.05, ++p < 0.01, and +++p < 0.001 versus the v/SB 206553 or v/Ro-60–0175 groups (Fisher's PLSD test).

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    Figure 4.

    Effect of 5,7-DHT lesion (a, b) or (±)-8-OH-DPAT administration (c, d) on SB 206553-induced DA release in the striatum and the nucleus accumbens. SB 206553 (5 mg/kg, i.p.) was administered alone (a, b) or 5 min after the subcutaneous injection of the 5-HT1A agonist 8-OH-DPAT (DPAT; 0.1 mg/kg) (c, d) (vertical arrows). Data represent mean ± SEM percentages of baseline (n = 4–6 animals/group).

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The Journal of Neuroscience: 24 (13)
Journal of Neuroscience
Vol. 24, Issue 13
31 Mar 2004
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Constitutive Activity of the Serotonin2C Receptor Inhibits In Vivo Dopamine Release in the Rat Striatum and Nucleus Accumbens
Philippe De Deurwaerdère, Sylvia Navailles, Kelly A Berg, William P. Clarke, Umberto Spampinato
Journal of Neuroscience 31 March 2004, 24 (13) 3235-3241; DOI: 10.1523/JNEUROSCI.0112-04.2004

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Constitutive Activity of the Serotonin2C Receptor Inhibits In Vivo Dopamine Release in the Rat Striatum and Nucleus Accumbens
Philippe De Deurwaerdère, Sylvia Navailles, Kelly A Berg, William P. Clarke, Umberto Spampinato
Journal of Neuroscience 31 March 2004, 24 (13) 3235-3241; DOI: 10.1523/JNEUROSCI.0112-04.2004
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