Prior chronic cocaine exposure in mice induces persistent alterations in cognitive function

Abstract

Chronic cocaine use has been proposed to induce long-lasting alterations in cognitive functions dependent on the prefrontal cortex, and these alterations may contribute to the development of addiction. However, the underlying cellular mechanisms remain largely unknown, in part because of the lack of suitable animal models of cocaine-induced cognitive dysfunction that are amenable to molecular manipulations. Here, we characterized the effects of repeated cocaine administration on multiple aspects of cognitive function in C57BL/6 mice. Mice received 14 daily injections of either cocaine or saline, followed by a drug-free period of 2 weeks. They were then assessed for (i) cognitive flexibility in an instrumental reversal learning task; (ii) attentional function and response inhibition in a three-choice serial reaction time task; and (iii) working memory in a delayed matching-to-position task. Prior chronic exposure to cocaine resulted in impairments in reversal learning and working memory. Although there were no effects on attentional function or response inhibition, a shift in the pattern of errors committed was observed. These results indicate that prior chronic cocaine exposure in mice induces long-lasting alterations in cognitive functions associated with the prefrontal cortex.