Neurochemical Correlates of Cocaine-Seeking Behaviour

Imaging studies in humans suggest that the amygdala plays an important role in craving elicited by cocaine and cocaine-conditioned environmental stimuli. The research examined the relationship between neurochemical changes in the amygdala and cocaine-seeking behavior following exposure to a cocaine-paired environment or a cocaine priming injection. It measured cocaine-seeking behavior by assessing the persistence of lever-pressing in the absence of cocaine reinforcement in animals previously trained to press a lever for cocaine infusions. Lever-pressing under these conditions is thought to reflect the incentive motivational properties of cocaine and cocaine-associated stimuli. It first investigated whether the pattern of changes in cocaine-seeking behavior corresponded with changes in concentrations of dopamine in dialysates obtained from the amygdala during the course of cocaine withdrawal.

There were concomitant changes in cocaine-seeking behavior and dialysate dopamine following the cocaine priming injection, but not following exposure alone to the cocaine self-administration environment. It next investigated changes in Fos protein expression as a general marker for neuronal activation. Exposure to the cocaine self-administration environment, but not the cocaine priming injection, elicited Fos expression in the basolateral nucleus of the amygdala, nucleus accumbens shell, and cingulate cortex. In contrast, the cocaine priming injection, but not the environmental stimuli, elicited Fos expression in the central nucleus of the amygdala and dorsolateral caudate-putamen.

The findings suggest that different neural mechanisms mediate cocaine-seeking behavior elicited by cocaine conditioned environmental stimuli and those elicited by a priming injection of cocaine. Increases in extracellular dopamine may be critical for the induction of cocaine-seeking behavior elicited by cocaine but may not be elicited by cocaine-conditioned environmental stimuli.

Source: Janet Neisewander, Ph.D., Arizona State University

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