Serotonin-3 receptor and ethanol-stimulated dopamine release in the nucleus accumbens

Serotonin-3 receptor and ethanol-stimulated dopamine release in the nucleus accumbens The present study was undertaken to examine the involvement of activation of 5-HT 3 receptors in the rat nucleus accumbens (Acb) on the effects of ethanol-induced increases of dopamine (DA) using the selective agonist 1-(m-chlorophenyl)-biguanide (CPBG). Perfusion of CPBG through the microdialysis probe concentration-dependently (3.3–100 μM) enhanced the extracellular levels of DA in the Acb. Extracellular DA concentrations increased as high as 1000% of baseline. The CPBG-induced increases in DA levels were Ca ++ dependent and inhibited by local perfusion with the 5-HT 3 antagonist ICS 205-930 (100 μM). In addition, CPBG at high concentrations caused significant decreases in the extracellular levels of DA metabolites. Intraperitoneal (IP) injection of 1 g/ kg ethanol produced no changes in extracellular DA levels in the Acb; coadministration of 1 g/kg ethanol (IP) and 5 μM CPBG (local) produced increases equal to 5 μM CPBG alone. Administration of 2 g/kg ethanol (IP) alone enhanced extracellular DA levels by ~60% above baseline, whereas local perfusion of 5 μM CPBG alone produced an increase of ~100% above baseline. The coadministration of 2 g/kg ethanol (IP) and 5 μM CPBG (local) enhanced DA levels by approximately 170% above baseline; this apparent additive enhancement was almost completely prevented when 100 μM ICS 205–930 was locally coperfused. Local administration of 3.3–100 μM CPBG did not alter the extracellular levels of serotonin or 5-hydroxyindoleacetic acid. The results support an involvement of 5-HT 3 receptors in regulating DA release in the Acb, and also in mediating ethanol-induced DA release. However, the in vivo interaction of ethanol and 5-HT at the 5-HT 3 receptor within the Acb is clearly not synergistic. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Pharmacology Biochemistry and Behavior Elsevier

Serotonin-3 receptor and ethanol-stimulated dopamine release in the nucleus accumbens

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Publisher
Elsevier
Copyright
Copyright © 1995 Elsevier Ltd
ISSN
0091-3057
eISSN
1873-5177
DOI
10.1016/0091-3057(95)00050-7
Publisher site
See Article on Publisher Site

Abstract

The present study was undertaken to examine the involvement of activation of 5-HT 3 receptors in the rat nucleus accumbens (Acb) on the effects of ethanol-induced increases of dopamine (DA) using the selective agonist 1-(m-chlorophenyl)-biguanide (CPBG). Perfusion of CPBG through the microdialysis probe concentration-dependently (3.3–100 μM) enhanced the extracellular levels of DA in the Acb. Extracellular DA concentrations increased as high as 1000% of baseline. The CPBG-induced increases in DA levels were Ca ++ dependent and inhibited by local perfusion with the 5-HT 3 antagonist ICS 205-930 (100 μM). In addition, CPBG at high concentrations caused significant decreases in the extracellular levels of DA metabolites. Intraperitoneal (IP) injection of 1 g/ kg ethanol produced no changes in extracellular DA levels in the Acb; coadministration of 1 g/kg ethanol (IP) and 5 μM CPBG (local) produced increases equal to 5 μM CPBG alone. Administration of 2 g/kg ethanol (IP) alone enhanced extracellular DA levels by ~60% above baseline, whereas local perfusion of 5 μM CPBG alone produced an increase of ~100% above baseline. The coadministration of 2 g/kg ethanol (IP) and 5 μM CPBG (local) enhanced DA levels by approximately 170% above baseline; this apparent additive enhancement was almost completely prevented when 100 μM ICS 205–930 was locally coperfused. Local administration of 3.3–100 μM CPBG did not alter the extracellular levels of serotonin or 5-hydroxyindoleacetic acid. The results support an involvement of 5-HT 3 receptors in regulating DA release in the Acb, and also in mediating ethanol-induced DA release. However, the in vivo interaction of ethanol and 5-HT at the 5-HT 3 receptor within the Acb is clearly not synergistic.

Journal

Pharmacology Biochemistry and BehaviorElsevier

Published: Aug 1, 1995

References

  • Presynaptic dopamine release is enhanced by 5-HT 3 receptor activation in medial prefrontal cortex of freely moving rats
    Chen, J.; Paredes, W.; van Praag, H.M.; Lowinson, J.H.; Gardner, E.L.
  • Blockade of the discriminative stimulus effects of ethanol with 5-HT 3 receptor antagonists
    Grant, K.A.; Barrett, J.E.
  • Quantitative autoradiographic mapping of 5-HT 3 receptors in the rat CNS using ( 125 I)iodo-zacopride and ( 3 H)zacopride as radioligands
    Laporte, A.M.; Koscielniak, T.; Ponchant, M.; Verge, D.; Hamon, M.; Gozlan, H.
  • Opposing roles for 5-HT 1B and 5-HT 3 receptors in the control of 5-HT release in rat hippocampus in vivo
    Martin, K.F.; Hannon, S.; Phillips, I.; Heal, D.J.
  • Ethanol enhances the release of dopamine and serotonin in the nucleus accumbens of HAD and LAD lines of rats
    Yoshimoto, K.; McBride, W.J.; Lumeng, L.; Li, T.K.

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