Reduction of adult hippocampal neurogenesis confers vulnerability in an animal model of cocaine addiction

Michele A. Noonan, Sarah E. Bulin, Dwain C. Fuller, Amelia J. Eisch

Research output: Contribution to journalArticle

140 Citations (Scopus)

Abstract

Drugs of abuse dynamically regulate adult neurogenesis, which appears important for some types of learning and memory. Interestingly, a major site of adult neurogenesis, the hippocampus, is important in the formation of drug- context associations and in the mediation of drug-taking and drug-seeking behaviors in animal models of addiction. Correlative evidence suggests an inverse relationship between hippocampal neurogenesis and drug-taking or drug-seeking behaviors, but the lack of a causative link has made the relationship between adult-generated neurons and addiction unclear. We used rat intravenous cocaine self-administration in rodents, a clinically relevant animal model of addiction, to test the hypothesis that suppression of adult hippocampal neurogenesis enhances vulnerability to addiction and relapse. Suppression of adult hippocampal neurogenesis via cranial irradiation before drug-taking significantly increased cocaine self-administration on both fixed-ratio and progressive-ratio schedules, as well as induced a vertical shift in the dose-response curve. This was not a general enhancement of learning, motivation, or locomotion, because sucrose self-administration and locomotor activity were unchanged in irradiated rats. Suppression of adult hippocampal neurogenesis after drug-taking significantly enhanced resistance to extinction of drug-seeking behavior. These studies identify reduced adult hippocampal neurogenesis as a novel risk factor for addiction-related behaviors in an animal model of cocaine addiction. Furthermore, they suggest that therapeutics to specifically increase or stabilize adult hippocampal neurogenesis could aid in preventing initial addiction as well as future relapse. Copyright

Original languageEnglish (US)
Pages (from-to)304-315
Number of pages12
JournalJournal of Neuroscience
Volume30
Issue number1
DOIs
StatePublished - Jan 6 2010

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Cocaine-Related Disorders
Neurogenesis
Animal Models
Drug-Seeking Behavior
Self Administration
Pharmaceutical Preparations
Locomotion
Cocaine
Learning
Cranial Irradiation
Recurrence
Street Drugs
Sucrose
Motivation
Rodentia
Hippocampus
Appointments and Schedules
Neurons

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Reduction of adult hippocampal neurogenesis confers vulnerability in an animal model of cocaine addiction. / Noonan, Michele A.; Bulin, Sarah E.; Fuller, Dwain C.; Eisch, Amelia J.

In: Journal of Neuroscience, Vol. 30, No. 1, 06.01.2010, p. 304-315.

Research output: Contribution to journalArticle

Noonan, Michele A. ; Bulin, Sarah E. ; Fuller, Dwain C. ; Eisch, Amelia J. / Reduction of adult hippocampal neurogenesis confers vulnerability in an animal model of cocaine addiction. In: Journal of Neuroscience. 2010 ; Vol. 30, No. 1. pp. 304-315.
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