Inhibition of nitric oxide synthase in the ventral tegmental area attenuates cocaine sensitization in rats

John J. Byrnes, Morten M. Pantke, Julie A. Onton, Ronald P Hammer

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

1. Male Sprague-Dawley rats were pretreated via bilateral infusion of the VTA with the selective neuronal nitric oxide synthase inhibitor, 7- nitroindazole (0, 8, or 40 ng/hemisphere), prior to each of 7 dally systemic cocaine (30 mg/kg, i.p.) or saline (1 ml/kg) treatments. 2. After a 7-day treatment withdrawal period, rats received a final systemic challenge with either cocaine (30 mg/kg, i.p.) or saline (1 ml/kg). 3. Locomotor and stereotypic activity were measured following the first and last treatments. 4. Daily cocaine treatment led to the development of sensitization to its stereotypic effects as revealed upon drug challenge. 5. The development of sensitization of cocaine-induced stereotypy was completely blocked by daily intra-VTA pretreatment with 7-nitroindazole. 6. In addition, attenuation of the locomotor effects of cocaine challenge was also observed in animals that received daily intra-VTA 7-nitroindazole (40 ng/hemisphere) infusions. 7. The results indicate that VTA nitric oxide is necessary for the development of sensitization of cocaine-induced stereotypic behavior, and that its repeated inhibition may produce lasting effects on the locomotor response to the drug.

Original languageEnglish (US)
Pages (from-to)261-273
Number of pages13
JournalProgress in Neuro-Psychopharmacology and Biological Psychiatry
Volume24
Issue number2
DOIs
StatePublished - Feb 2000
Externally publishedYes

Fingerprint

Ventral Tegmental Area
Cocaine
Nitric Oxide Synthase
Nitric Oxide Synthase Type I
Locomotion
Pharmaceutical Preparations
Sprague Dawley Rats
Inhibition (Psychology)
Nitric Oxide
7-nitroindazole

Keywords

  • 7- nitroindazole
  • Behavioral sensitization
  • Cocaine
  • Nitric oxide synthase
  • Ventral tegmental area

ASJC Scopus subject areas

  • Biological Psychiatry
  • Pharmacology

Cite this

Inhibition of nitric oxide synthase in the ventral tegmental area attenuates cocaine sensitization in rats. / Byrnes, John J.; Pantke, Morten M.; Onton, Julie A.; Hammer, Ronald P.

In: Progress in Neuro-Psychopharmacology and Biological Psychiatry, Vol. 24, No. 2, 02.2000, p. 261-273.

Research output: Contribution to journalArticle

@article{c056a4a58bf64c238b320215637a9626,
title = "Inhibition of nitric oxide synthase in the ventral tegmental area attenuates cocaine sensitization in rats",
abstract = "1. Male Sprague-Dawley rats were pretreated via bilateral infusion of the VTA with the selective neuronal nitric oxide synthase inhibitor, 7- nitroindazole (0, 8, or 40 ng/hemisphere), prior to each of 7 dally systemic cocaine (30 mg/kg, i.p.) or saline (1 ml/kg) treatments. 2. After a 7-day treatment withdrawal period, rats received a final systemic challenge with either cocaine (30 mg/kg, i.p.) or saline (1 ml/kg). 3. Locomotor and stereotypic activity were measured following the first and last treatments. 4. Daily cocaine treatment led to the development of sensitization to its stereotypic effects as revealed upon drug challenge. 5. The development of sensitization of cocaine-induced stereotypy was completely blocked by daily intra-VTA pretreatment with 7-nitroindazole. 6. In addition, attenuation of the locomotor effects of cocaine challenge was also observed in animals that received daily intra-VTA 7-nitroindazole (40 ng/hemisphere) infusions. 7. The results indicate that VTA nitric oxide is necessary for the development of sensitization of cocaine-induced stereotypic behavior, and that its repeated inhibition may produce lasting effects on the locomotor response to the drug.",
keywords = "7- nitroindazole, Behavioral sensitization, Cocaine, Nitric oxide synthase, Ventral tegmental area",
author = "Byrnes, {John J.} and Pantke, {Morten M.} and Onton, {Julie A.} and Hammer, {Ronald P}",
year = "2000",
month = "2",
doi = "10.1016/S0278-5846(99)00094-9",
language = "English (US)",
volume = "24",
pages = "261--273",
journal = "Progress in Neuro-Psychopharmacology and Biological Psychiatry",
issn = "0278-5846",
publisher = "Elsevier Inc.",
number = "2",

}

TY - JOUR

T1 - Inhibition of nitric oxide synthase in the ventral tegmental area attenuates cocaine sensitization in rats

AU - Byrnes, John J.

AU - Pantke, Morten M.

AU - Onton, Julie A.

AU - Hammer, Ronald P

PY - 2000/2

Y1 - 2000/2

N2 - 1. Male Sprague-Dawley rats were pretreated via bilateral infusion of the VTA with the selective neuronal nitric oxide synthase inhibitor, 7- nitroindazole (0, 8, or 40 ng/hemisphere), prior to each of 7 dally systemic cocaine (30 mg/kg, i.p.) or saline (1 ml/kg) treatments. 2. After a 7-day treatment withdrawal period, rats received a final systemic challenge with either cocaine (30 mg/kg, i.p.) or saline (1 ml/kg). 3. Locomotor and stereotypic activity were measured following the first and last treatments. 4. Daily cocaine treatment led to the development of sensitization to its stereotypic effects as revealed upon drug challenge. 5. The development of sensitization of cocaine-induced stereotypy was completely blocked by daily intra-VTA pretreatment with 7-nitroindazole. 6. In addition, attenuation of the locomotor effects of cocaine challenge was also observed in animals that received daily intra-VTA 7-nitroindazole (40 ng/hemisphere) infusions. 7. The results indicate that VTA nitric oxide is necessary for the development of sensitization of cocaine-induced stereotypic behavior, and that its repeated inhibition may produce lasting effects on the locomotor response to the drug.

AB - 1. Male Sprague-Dawley rats were pretreated via bilateral infusion of the VTA with the selective neuronal nitric oxide synthase inhibitor, 7- nitroindazole (0, 8, or 40 ng/hemisphere), prior to each of 7 dally systemic cocaine (30 mg/kg, i.p.) or saline (1 ml/kg) treatments. 2. After a 7-day treatment withdrawal period, rats received a final systemic challenge with either cocaine (30 mg/kg, i.p.) or saline (1 ml/kg). 3. Locomotor and stereotypic activity were measured following the first and last treatments. 4. Daily cocaine treatment led to the development of sensitization to its stereotypic effects as revealed upon drug challenge. 5. The development of sensitization of cocaine-induced stereotypy was completely blocked by daily intra-VTA pretreatment with 7-nitroindazole. 6. In addition, attenuation of the locomotor effects of cocaine challenge was also observed in animals that received daily intra-VTA 7-nitroindazole (40 ng/hemisphere) infusions. 7. The results indicate that VTA nitric oxide is necessary for the development of sensitization of cocaine-induced stereotypic behavior, and that its repeated inhibition may produce lasting effects on the locomotor response to the drug.

KW - 7- nitroindazole

KW - Behavioral sensitization

KW - Cocaine

KW - Nitric oxide synthase

KW - Ventral tegmental area

UR - http://www.scopus.com/inward/record.url?scp=0034144419&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034144419&partnerID=8YFLogxK

U2 - 10.1016/S0278-5846(99)00094-9

DO - 10.1016/S0278-5846(99)00094-9

M3 - Article

VL - 24

SP - 261

EP - 273

JO - Progress in Neuro-Psychopharmacology and Biological Psychiatry

JF - Progress in Neuro-Psychopharmacology and Biological Psychiatry

SN - 0278-5846

IS - 2

ER -