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

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.

Intolerance of uncertainty modulates the insensitivity to reinforcer devaluation found in an avoidance task

The reinforcer devaluation paradigm has been regarded as a canonical paradigm to detect habit-like behavior in animal and human instrumental learning. Though less studied, avoidance situations set a scenario where habit-like behavior may be of great experimental and clinical interest. On the other hand, proactive intolerance of uncertainty has been shown as a factor facilitating responses in uncertain situations. Thus, avoidance situations in which uncertainty is favoured, may be taken as a relevant paradigm to examine the role of intolerance of uncertainty as a facilitatory factor for habit-like behavior to occur. In our experiment we used a free-operant discriminative avoidance procedure to implement a devaluation paradigm. Participants learned to avoid an aversive noise presented either to the right or to the left ear by pressing two different keys. After a devaluation phase where the volume of one of the noises was reduced, they went through a test phase identical to the avoidance phase except for the fact that the noise was never administered. Sensitivity to reinforcer devaluation was examined by comparing the response rate to the cue associated to the devalued reinforcer with that to the cue associated to the still aversive reinforcer. The results showed that intolerance of uncertainty was positively associated to insensitivity to reinforcer devaluation. Finally, we discuss the theoretical and clinical implications of the habit-like behavior obtained in our avoidance procedure.