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Behavioral traits predicting cocaine-conditioned place reference in mice: role of anxiety adn the basolateral amygdala

Ladrón de Guevara-Miranda, David,Pavón-Morón, Francisco Javier,Serrano, Antonia,Rivera-González, Patricia,Estivill-Torrús, Guillermo,Suárez-Pérez, Juan,Rodriguez-de-Fonseca, Fernando,Santín-Núñez, Luis Javier,Castilla-Ortega, María Estela

Abstract

Aims. The individual susceptibility to cocaine addiction, a factor of interest in the understanding and prevention of this disorder, may be predicted by certain behavioral traits. However, these are not usually taken into account in research, making it difficult to identify whether they are a cause or a consequence of drug use. Methods. Male C57BL/6J mice underwent a battery of behavioral tests (elevated plus maze, hole-board, novelty preference in the Y maze, episodic-like object recognition memory and forced swimming test), followed by a cocaine-conditioned place preference (CPP) training to assess the reinforcing effect of the drug. In a second study, we aimed to determine the existence of neurobiological differences between the mice expressing high or low CPP by studying the number of neurons in certain addiction-related structures: the medial prefrontal cortex, the basolateral amygdala and the ventral tegmental area. Results. Anxiety-like behaviors in the elevated plus maze successfully predicted the cocaine-CPP behavior, so that the most anxious mice were also more likely to search for cocaine in a CPP paradigm. In addition, these mice exhibited an increased number of neurons in the basolateral amygdala, a key structure in emotional response including anxiety expression, without differences in the others regions analyzed. Conclusions. Our results suggest a relevant role of anxiety as a psychological risk factor for cocaine vulnerability, with the basolateral amygdala as potential common neural center for both anxiety and addiction.

Full text

BEHAVIORAL TRAITS PREDICTING COCAINE-CONDITIONED PLACE PREFERENCE IN MICE: ROLE OF ANXIETY AND THE BASOLATERAL AMYGDALA David Ladrón de Guevara-Miranda, Francisco J. Pavón, Antonia Serrano, Patricia Rivera, Guillermo Estivill-Torrús, Juan Suárez, Fernando Rodríguez de Fonseca, Luis J Santín, Estela Castilla-Ortega Aims. The individual susceptibility to cocaine addiction, a factor of interest in the understanding and prevention of this disorder, may be predicted by certain behavioral traits. However, these are not usually taken into account in research, making it difficult to identify whether they are a cause or a consequence of drug use. Methods. Male C57BL/6J mice underwent a battery of behavioral tests (elevated plus maze, hole-board, novelty preference in the Y maze, episodic-like object recognition memory and forced swimming test), followed by a cocaine-conditioned place preference (CPP) training to assess the reinforcing effect of the drug. In a second study, we aimed to determine the existence of neurobiological differences between the mice expressing high or low CPP by studying the number of neurons in certain addiction-related structures: the medial prefrontal cortex, the basolateral amygdala and the ventral tegmental area. Results. Anxiety-like behaviors in the elevated plus maze successfully predicted the cocaine-CPP behavior, so that the most anxious mice were also more likely to search for cocaine in a CPP paradigm. In addition, these mice exhibited an increased number of neurons in the basolateral amygdala, a key structure in emotional response including anxiety expression, without differences in the others regions analyzed. Conclusions. Our results suggest a relevant role of anxiety as a psychological risk factor for cocaine vulnerability, with the basolateral amygdala as potential common neural center for both anxiety and addiction. Funding: PSI2013-44901-P, FPU13/04819, CD12/00455, Red de Trastornos Adictivos and Universidad de Málaga, Campus de Excelencia Internacional Andalucía Tech. Instituto de Investigación Biomédica de Málaga (IBIMA) – Hospital Regional Universitario de Málaga – Spain Email: [email protected], [email protected], [email protected], [email protected], [email protected], [email protected], [email protected], [email protected], estel[email protected]