The 5-HT3 antagonist zacopride attenuates cocaine-induced increases in extracellular dopamine in rat nucleus accumbens

Charles S. McNeish, Adena L. Svingos, Robert Hitzemann, Robert E. Strecker

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Pretreatment with the serotonin-3 (5-HT3) antagonist racemic (±)-Zacopride hydrochloride (ZAC, 0.1 mg/kg, IP) has been previously found to completely abolish the locomotor activity induced by cocaine (10 mg/kg, IP). To determine if this effect was mediated by fluctuations in the extracellular levels of forebrain dopamine (DA), we examined the ability of ZAC to attenuate cocaine-induced increases in extracellular DA levels. Microdialysis samples were collected from the nucleus accumbens region (NAS) of awake, male, Sprague-Dawley rats. ZAC treatment alone (0.1 mg/kg, IP) did not alter DA levels relative to baseline. However, this dose of ZAC given 1 h prior to cocaine challenge (10 mg/kg, IP) caused a 27% reduction in the peak level of extracellular DA produced by cocaine, relative to saline-pretreated control animals. These results suggest that the ability of ZAC to attenuate cocaine-induced increases in extracellular DA levels may contribute to ZAC's ability to suppress cocaine-induced locomotor activity in the rat. However, additional neurochemical mechanisms are likely to be important in mediating the robust behavioral effects previously reported.

Original languageEnglish (US)
Pages (from-to)759-763
Number of pages5
JournalPharmacology, Biochemistry and Behavior
Volume45
Issue number4
DOIs
StatePublished - 1993
Externally publishedYes

Fingerprint

Serotonin 5-HT3 Receptor Antagonists
Nucleus Accumbens
Cocaine
Rats
Dopamine
Locomotion
Microdialysis
Prosencephalon
Sprague Dawley Rats
zacopride
Serotonin
Animals

Keywords

  • Cocaine
  • Dopamine release
  • Microdialysis
  • Nucleus accumbens
  • Rat
  • Serotonin-3 receptor
  • Zacopride

ASJC Scopus subject areas

  • Biochemistry
  • Behavioral Neuroscience
  • Pharmacology

Cite this

The 5-HT3 antagonist zacopride attenuates cocaine-induced increases in extracellular dopamine in rat nucleus accumbens. / McNeish, Charles S.; Svingos, Adena L.; Hitzemann, Robert; Strecker, Robert E.

In: Pharmacology, Biochemistry and Behavior, Vol. 45, No. 4, 1993, p. 759-763.

Research output: Contribution to journalArticle

@article{c678b977265941b891b2b27ec7de52ee,
title = "The 5-HT3 antagonist zacopride attenuates cocaine-induced increases in extracellular dopamine in rat nucleus accumbens",
abstract = "Pretreatment with the serotonin-3 (5-HT3) antagonist racemic (±)-Zacopride hydrochloride (ZAC, 0.1 mg/kg, IP) has been previously found to completely abolish the locomotor activity induced by cocaine (10 mg/kg, IP). To determine if this effect was mediated by fluctuations in the extracellular levels of forebrain dopamine (DA), we examined the ability of ZAC to attenuate cocaine-induced increases in extracellular DA levels. Microdialysis samples were collected from the nucleus accumbens region (NAS) of awake, male, Sprague-Dawley rats. ZAC treatment alone (0.1 mg/kg, IP) did not alter DA levels relative to baseline. However, this dose of ZAC given 1 h prior to cocaine challenge (10 mg/kg, IP) caused a 27{\%} reduction in the peak level of extracellular DA produced by cocaine, relative to saline-pretreated control animals. These results suggest that the ability of ZAC to attenuate cocaine-induced increases in extracellular DA levels may contribute to ZAC's ability to suppress cocaine-induced locomotor activity in the rat. However, additional neurochemical mechanisms are likely to be important in mediating the robust behavioral effects previously reported.",
keywords = "Cocaine, Dopamine release, Microdialysis, Nucleus accumbens, Rat, Serotonin-3 receptor, Zacopride",
author = "McNeish, {Charles S.} and Svingos, {Adena L.} and Robert Hitzemann and Strecker, {Robert E.}",
year = "1993",
doi = "10.1016/0091-3057(93)90118-D",
language = "English (US)",
volume = "45",
pages = "759--763",
journal = "Pharmacology Biochemistry and Behavior",
issn = "0091-3057",
publisher = "Elsevier Inc.",
number = "4",

}

TY - JOUR

T1 - The 5-HT3 antagonist zacopride attenuates cocaine-induced increases in extracellular dopamine in rat nucleus accumbens

AU - McNeish, Charles S.

AU - Svingos, Adena L.

AU - Hitzemann, Robert

AU - Strecker, Robert E.

PY - 1993

Y1 - 1993

N2 - Pretreatment with the serotonin-3 (5-HT3) antagonist racemic (±)-Zacopride hydrochloride (ZAC, 0.1 mg/kg, IP) has been previously found to completely abolish the locomotor activity induced by cocaine (10 mg/kg, IP). To determine if this effect was mediated by fluctuations in the extracellular levels of forebrain dopamine (DA), we examined the ability of ZAC to attenuate cocaine-induced increases in extracellular DA levels. Microdialysis samples were collected from the nucleus accumbens region (NAS) of awake, male, Sprague-Dawley rats. ZAC treatment alone (0.1 mg/kg, IP) did not alter DA levels relative to baseline. However, this dose of ZAC given 1 h prior to cocaine challenge (10 mg/kg, IP) caused a 27% reduction in the peak level of extracellular DA produced by cocaine, relative to saline-pretreated control animals. These results suggest that the ability of ZAC to attenuate cocaine-induced increases in extracellular DA levels may contribute to ZAC's ability to suppress cocaine-induced locomotor activity in the rat. However, additional neurochemical mechanisms are likely to be important in mediating the robust behavioral effects previously reported.

AB - Pretreatment with the serotonin-3 (5-HT3) antagonist racemic (±)-Zacopride hydrochloride (ZAC, 0.1 mg/kg, IP) has been previously found to completely abolish the locomotor activity induced by cocaine (10 mg/kg, IP). To determine if this effect was mediated by fluctuations in the extracellular levels of forebrain dopamine (DA), we examined the ability of ZAC to attenuate cocaine-induced increases in extracellular DA levels. Microdialysis samples were collected from the nucleus accumbens region (NAS) of awake, male, Sprague-Dawley rats. ZAC treatment alone (0.1 mg/kg, IP) did not alter DA levels relative to baseline. However, this dose of ZAC given 1 h prior to cocaine challenge (10 mg/kg, IP) caused a 27% reduction in the peak level of extracellular DA produced by cocaine, relative to saline-pretreated control animals. These results suggest that the ability of ZAC to attenuate cocaine-induced increases in extracellular DA levels may contribute to ZAC's ability to suppress cocaine-induced locomotor activity in the rat. However, additional neurochemical mechanisms are likely to be important in mediating the robust behavioral effects previously reported.

KW - Cocaine

KW - Dopamine release

KW - Microdialysis

KW - Nucleus accumbens

KW - Rat

KW - Serotonin-3 receptor

KW - Zacopride

UR - http://www.scopus.com/inward/record.url?scp=0027338317&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027338317&partnerID=8YFLogxK

U2 - 10.1016/0091-3057(93)90118-D

DO - 10.1016/0091-3057(93)90118-D

M3 - Article

VL - 45

SP - 759

EP - 763

JO - Pharmacology Biochemistry and Behavior

JF - Pharmacology Biochemistry and Behavior

SN - 0091-3057

IS - 4

ER -