Dopamine depletion in the medial prefrontal cortex induces sensitized- like behavioral and neurochemical responses to cocaine

Chad E. Beyer, Jeffery Steketee

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

It has been postulated that behavioral sensitization to cocaine is associated with an attenuation of cocaine-induced dopamine (DA) transmission in the medial prefrontal cortex (mPFC). Hence, experiments were designed to examine the effects of chemically-induced cortical DA depletion on the acute behavioral and neurochemical responses to cocaine. One week following two bilateral 6-hydroxydopamine (6-OHDA) injections into the mPFC, animals received injections of cocaine (7.5, 15 or 30 mg/kg, i.p.) or saline (1 ml/kg, i.p.) in a randomized fashion with a minimum 3 day intertrial interval. Cocaine produced a dose-dependent increase in motor activity which was significantly enhanced in animals depleted (mean of 76%) of dopamine in the mPFC. Likewise, 6-OHDA lesions of the mPFC produced a significant enhancement of cocaine-induced DA transmission in the nucleus accumbens (NAC) as estimated by in vivo microdialysis. These data indicate a permissive involvement of cortical DA in mediating behavioral and neurochemical responses to cocaine, as well as confirm the ability of the mPFC to influence subcortical structures in response to an acute injection of cocaine. Collectively, the present findings suggest that alterations in cortical DA transmission may be a neural substrate mediating the development of sensitization to cocaine, and thus, may contribute to the addictive properties of cocaine.

Original languageEnglish (US)
Pages (from-to)133-141
Number of pages9
JournalBrain Research
Volume833
Issue number2
DOIs
StatePublished - Jul 3 1999
Externally publishedYes

Fingerprint

Prefrontal Cortex
Cocaine
Dopamine
Oxidopamine
Injections
Aptitude
Microdialysis
Nucleus Accumbens
Motor Activity

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

Cite this

Dopamine depletion in the medial prefrontal cortex induces sensitized- like behavioral and neurochemical responses to cocaine. / Beyer, Chad E.; Steketee, Jeffery.

In: Brain Research, Vol. 833, No. 2, 03.07.1999, p. 133-141.

Research output: Contribution to journalArticle

@article{e9ab2af31dfa4f01a18ccae971ee18e9,
title = "Dopamine depletion in the medial prefrontal cortex induces sensitized- like behavioral and neurochemical responses to cocaine",
abstract = "It has been postulated that behavioral sensitization to cocaine is associated with an attenuation of cocaine-induced dopamine (DA) transmission in the medial prefrontal cortex (mPFC). Hence, experiments were designed to examine the effects of chemically-induced cortical DA depletion on the acute behavioral and neurochemical responses to cocaine. One week following two bilateral 6-hydroxydopamine (6-OHDA) injections into the mPFC, animals received injections of cocaine (7.5, 15 or 30 mg/kg, i.p.) or saline (1 ml/kg, i.p.) in a randomized fashion with a minimum 3 day intertrial interval. Cocaine produced a dose-dependent increase in motor activity which was significantly enhanced in animals depleted (mean of 76{\%}) of dopamine in the mPFC. Likewise, 6-OHDA lesions of the mPFC produced a significant enhancement of cocaine-induced DA transmission in the nucleus accumbens (NAC) as estimated by in vivo microdialysis. These data indicate a permissive involvement of cortical DA in mediating behavioral and neurochemical responses to cocaine, as well as confirm the ability of the mPFC to influence subcortical structures in response to an acute injection of cocaine. Collectively, the present findings suggest that alterations in cortical DA transmission may be a neural substrate mediating the development of sensitization to cocaine, and thus, may contribute to the addictive properties of cocaine.",
author = "Beyer, {Chad E.} and Jeffery Steketee",
year = "1999",
month = "7",
day = "3",
doi = "10.1016/S0006-8993(99)01485-7",
language = "English (US)",
volume = "833",
pages = "133--141",
journal = "Brain Research",
issn = "0006-8993",
publisher = "Elsevier",
number = "2",

}

TY - JOUR

T1 - Dopamine depletion in the medial prefrontal cortex induces sensitized- like behavioral and neurochemical responses to cocaine

AU - Beyer, Chad E.

AU - Steketee, Jeffery

PY - 1999/7/3

Y1 - 1999/7/3

N2 - It has been postulated that behavioral sensitization to cocaine is associated with an attenuation of cocaine-induced dopamine (DA) transmission in the medial prefrontal cortex (mPFC). Hence, experiments were designed to examine the effects of chemically-induced cortical DA depletion on the acute behavioral and neurochemical responses to cocaine. One week following two bilateral 6-hydroxydopamine (6-OHDA) injections into the mPFC, animals received injections of cocaine (7.5, 15 or 30 mg/kg, i.p.) or saline (1 ml/kg, i.p.) in a randomized fashion with a minimum 3 day intertrial interval. Cocaine produced a dose-dependent increase in motor activity which was significantly enhanced in animals depleted (mean of 76%) of dopamine in the mPFC. Likewise, 6-OHDA lesions of the mPFC produced a significant enhancement of cocaine-induced DA transmission in the nucleus accumbens (NAC) as estimated by in vivo microdialysis. These data indicate a permissive involvement of cortical DA in mediating behavioral and neurochemical responses to cocaine, as well as confirm the ability of the mPFC to influence subcortical structures in response to an acute injection of cocaine. Collectively, the present findings suggest that alterations in cortical DA transmission may be a neural substrate mediating the development of sensitization to cocaine, and thus, may contribute to the addictive properties of cocaine.

AB - It has been postulated that behavioral sensitization to cocaine is associated with an attenuation of cocaine-induced dopamine (DA) transmission in the medial prefrontal cortex (mPFC). Hence, experiments were designed to examine the effects of chemically-induced cortical DA depletion on the acute behavioral and neurochemical responses to cocaine. One week following two bilateral 6-hydroxydopamine (6-OHDA) injections into the mPFC, animals received injections of cocaine (7.5, 15 or 30 mg/kg, i.p.) or saline (1 ml/kg, i.p.) in a randomized fashion with a minimum 3 day intertrial interval. Cocaine produced a dose-dependent increase in motor activity which was significantly enhanced in animals depleted (mean of 76%) of dopamine in the mPFC. Likewise, 6-OHDA lesions of the mPFC produced a significant enhancement of cocaine-induced DA transmission in the nucleus accumbens (NAC) as estimated by in vivo microdialysis. These data indicate a permissive involvement of cortical DA in mediating behavioral and neurochemical responses to cocaine, as well as confirm the ability of the mPFC to influence subcortical structures in response to an acute injection of cocaine. Collectively, the present findings suggest that alterations in cortical DA transmission may be a neural substrate mediating the development of sensitization to cocaine, and thus, may contribute to the addictive properties of cocaine.

UR - http://www.scopus.com/inward/record.url?scp=0033519887&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033519887&partnerID=8YFLogxK

U2 - 10.1016/S0006-8993(99)01485-7

DO - 10.1016/S0006-8993(99)01485-7

M3 - Article

VL - 833

SP - 133

EP - 141

JO - Brain Research

JF - Brain Research

SN - 0006-8993

IS - 2

ER -