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Blockade of D2 dopamine receptors in the VTA induces a long-lasting enhancement of the locomotor activating effects of amphetamine

Academic Article
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Overview

authors

  • Tanabe, L. M.
  • Suto, Nobuyoshi
  • Creekmore, E.
  • Steinmiller, C. L.
  • Vezina, P.

publication date

  • September 2004

journal

  • Behavioural Pharmacology  Journal

abstract

  • The present study examined the effects of pre-exposure to eticlopride, a D2 dopamine receptor antagonist, in the ventral tegmental area (VTA) on the subsequent locomotor activating effects of amphetamine (AMPH). Rats were pre-exposed to one of three doses of eticlopride (0.75, 3.0 or 12.0 microg/0.5 microl per side) or saline (0.5 microl/side) in the VTA, once every third day, for a total of three infusions. Locomotor activity was recorded for 2 h following each pre-exposure injection. The low and intermediate doses of eticlopride produced no effects, while the high dose decreased locomotor activity compared to saline controls. 10-14 days following the last pre-exposure injection, all rats were challenged with AMPH (1.0 mg/kg, ip) and locomotor activity was recorded. Rats pre-exposed to the low dose of eticlopride exhibited enhanced locomotor activity whereas those pre-exposed to the intermediate or high doses did not differ from saline pre-exposed controls, suggesting that blockade of D2 dopamine receptors in the VTA can lead to sensitized locomotor responding to AMPH. To investigate the possible mechanism by which the low dose of eticlopride induced sensitization, extracellular levels of dopamine were measured as increasing concentrations of eticlopride (0.1, 1.0, 10.0 and 100.0 micromol/l) were perfused through a microdialysis probe implanted in the VTA. Only the lowest eticlopride concentration elevated extracellular dopamine levels. Therefore, as in the case of AMPH-induced sensitization, the induction by eticlopride of sensitization to AMPH may be initiated by the ability of eticlopride to increase extracellular levels of dopamine in the VTA.

subject areas

  • Amphetamine
  • Animals
  • Central Nervous System Stimulants
  • Dopamine
  • Dopamine Antagonists
  • Dose-Response Relationship, Drug
  • Male
  • Motor Activity
  • Rats
  • Rats, Long-Evans
  • Receptors, Dopamine D2
  • Salicylamides
  • Ventral Tegmental Area
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Research

keywords

  • D-2 dopamine receptor
  • amphetamine
  • eticlopride
  • rat
  • sensitization
  • ventral segmental area
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Identity

International Standard Serial Number (ISSN)

  • 0955-8810 (Print) 0955-8810 (Linking)

PubMed ID

  • 15343065
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Additional Document Info

start page

  • 387

end page

  • 395

volume

  • 15

issue

  • 5-6

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