Prefrontocortical dopamine loss in rats delays long-term extinction of contextual conditioned fear, and reduces social interaction with out affecting short-term social interaction memory

Abstract

Prefrontaldopamine loss delays extinction of cued fear conditioning responses, but its role in contextualfear conditioning has not been explored. Medialprefrontallesions also enhance socialinteraction in rats, but the role of prefrontaldopamine loss on social interaction memory is not known. Besides, a role for subcorticalaccumbaldopamine on mnesic changes after prefrontaldopamine manipulation has been proposed but not explored. The objective was to study the involvement of dopaminergic neuro transmission in the medial prefrontalcortex (mPFC) and nucleus accumbens in two mnesic tasks: contextual fear conditioning and social interaction memory. For contextual fear conditioning, short- and long-term freezing responses alter an electric shock were studied, as wellas extinction retention. Regarding socialinteraction memory, the recognition of a juvenile, a very sensitive short-term memory test, was used. Dopamine loss was carried out by injection of 6-hydroxydopamine, and postmortem catecholamine levels were analyzed by high-performance liquid chromatography. Prefrontocorticaldopamine loss (>76%) led to a reactive enhancement of accumbaldopamine content (p<0.01), supporting the hypothesis that a hyperdopaminergic tone emerges in the nucleus accumbens after prefrontocorticaldopamine loss. In lesioned rats, long-term extinction of contextualfear conditioning was significantly delayed and extinction retention was impaired without changes in acquisition and short-term contextualfear conditioning and, on the other hand, acquisition and short-term socialinteraction memory were not affected, although time spent on socialinteraction was significantly reduced. Added dopamine loss in the nucleus accumbens (>76%) did not alter these behavioralchanges. In summary, the results of the present study indicate that the dopaminergic network in the mPFC (but not in the nucleus accumbens) coordinates the normallong-term extinction of contextualfear conditioning responses without affecting their acquisition, and it is involved in time spent on socialinteraction, but not acquisition and short-term social interaction memory. © 2003 Nature Publishing Group.