Depleting adult dentate gyrus neurogenesis increases cocaine-seeking behavior

• Published in: Molecular psychiatry Vol. 24; no. 2; pp. 312 - 320
• Main Authors: Deroche-Gamonet, Véronique, Revest, Jean-Michel, Fiancette, Jean-François, Balado, Eric, Koehl, Muriel, Grosjean, Noëlle, Abrous, Djoher Nora, Piazza, Pier-Vincenzo
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.02.2019; Nature Publishing Group
• Subjects: 13/1; 14/19; 42/41; 42/44; 631/208; 631/378; 631/443; 631/61; 64/60; 82/51; Addiction; Adults; Animal genetic engineering; Animals; Behavioral Sciences; Biological Psychology; Brain; Cocaine; Cocaine - metabolism; Cocaine-Related Disorders - physiopathology; Cues; Dentate gyrus; Dentate Gyrus - metabolism; Depletion; Drug abuse; Drug addiction; Drug self-administration; Drug-Seeking Behavior - physiology; Genetic engineering; Hippocampus; Hippocampus - physiopathology; Life Sciences; Male; Medicine; Medicine & Public Health; Memory; Memory - physiology; Mental disorders; Mice; Mice, Transgenic; Mood; Motivation; Narcotics; Neurogenesis; Neurogenesis - physiology; Neurons; Neurons and Cognition; Neurosciences; Pharmacotherapy; Psychiatry; Psychological aspects; Rodents; Self Administration; Transgenic mice
• ISSN: 1359-4184; 1476-5578
• DOI: 10.1038/s41380-018-0038-0

The hippocampus is the main locus for adult dentate gyrus (DG) neurogenesis. A number of studies have shown that aberrant DG neurogenesis correlates with many neuropsychiatric disorders, including drug addiction. Although clear causal relationships have been established between DG neurogenesis and memory dysfunction or mood-related disorders, evidence of the causal role of DG neurogenesis in drug-seeking behaviors has not been established. Here we assessed the role of new DG neurons in cocaine self-administration using an inducible transgenic approach that selectively depletes adult DG neurogenesis. Our results show that transgenic mice with decreased adult DG neurogenesis exhibit increased motivation to self-administer cocaine and a higher seeking response to cocaine-related cues. These results identify adult hippocampal neurogenesis as a key factor in vulnerability to cocaine addiction.