title: Cocaine-conditioned place preference is predicted by previous anxiety-like behavior and is related to an increased number of neurons in the basolateral amygdala.
abstract: The identification of behavioral traits that could predict an individual's susceptibility to engage in cocaine addiction is relevant for understanding and preventing this disorder, but investigations of cocaine addicts rarely allow us to determinate whether their behavioral attributes are a cause or a consequence of drug use. To study the behaviors that predict cocaine vulnerability, male C57BL/6J mice were examined in a battery of tests (the elevated plus maze, hole-board, novelty preference in the Y-Maze, episodic-like object recognition and forced swimming) prior to training in a cocaine-conditioned place preference (CPP) paradigm to assess the reinforcing value of the drug. In a second study, the anatomical basis of high and low CPP in the mouse brain was investigated by studying the number of neurons (neuronal nuclei-positive) in two addiction-related limbic regions (the medial prefrontal cortex and the basolateral amygdala) and the number of dopaminergic neurons (tyrosine hydroxylase-positive) in the ventral tegmental area by immunohistochemistry and stereology. Correlational analyses revealed that CPP behavior was successfully predicted by anxiety-like measures in the elevated plus maze (i.e., the more anxious mice showed more preference for the cocaine-paired compartment) but not by the other behaviors analyzed. In addition, increased numbers of neurons were found in the basolateral amygdala of the high CPP mice, a key brain center for anxiety and fear responses. The results support the theory that anxiety is a relevant factor for cocaine vulnerability, and the basolateral amygdala is a potential neurobiological substrate where both anxiety and cocaine vulnerability could overlap.
authors.affiliation: Departamento de Psicobiología y Metodología de las Ciencias del Comportamiento, Instituto de Investigación Biomédica de Málaga (IBIMA), Facultad de Psicología, Universidad de Málaga, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Ladrón de Guevara-Miranda
authors.affiliation: Unidad de Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Pavón
authors.affiliation: Unidad de Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Spain.
authors.forename: Antonia
authors.initials: A
authors.lastname: Serrano
authors.affiliation: Unidad de Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Rivera
authors.affiliation: Unidad de Gestión Clínica Intercentros de Neurociencias, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospitales Universitarios Regional de Málaga y Virgen de la Victoria, Spain.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Estivill-Torrús
authors.affiliation: Unidad de Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Suárez
authors.affiliation: Unidad de Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Rodríguez de Fonseca
authors.affiliation: Departamento de Psicobiología y Metodología de las Ciencias del Comportamiento, Instituto de Investigación Biomédica de Málaga (IBIMA), Facultad de Psicología, Universidad de Málaga, Spain. Electronic address: luis@uma.es.
authors.forename: Luis J
authors.initials: LJ
authors.lastname: Santín
authors.affiliation: Unidad de Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Spain. Electronic address: estela.castilla@ibima.eu.
authors.forename: Estela
authors.initials: E
authors.lastname: Castilla-Ortega
mesh_terms: D000818:Animals; D001007:Anxiety / Q000503:physiopathology*; D066272:Basolateral Nuclear Complex / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D002452:Cell Count; D003042:Cocaine / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000175:diagnosis / Q000473:pathology / Q000503:physiopathology; D003213:Conditioning, Psychological / Q000187:drug effects* / Q000502:physiology; D004195:Disease Models, Animal; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D007150:Immunohistochemistry; D008297:Male; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D011379:Prognosis; D013037:Spatial Behavior / Q000187:drug effects / Q000502:physiology
chemical_list: D018765:Dopamine Uptake Inhibitors; D003042:Cocaine
keywords: Cocaine addiction vulnerability traits; Elevated plus maze; Medial prefrontal cortex; Principal components factorial analysis PCA; Ventral tegmental area