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As a result of living in an enriched environment, the brain of animals undergoes molecular and morphological changes leading to improvements in learning and memory. These improvements correlate well with increase in neurogenesis, synaptic density, or neurotrophic factors. We review here, in the context of the literature, the experiments performed in our own laboratory on the effects of environmental enrichment on the dynamics of dopamine and acetylcholine in the prefrontal cortex under a situation of acute mild stress. In these last studies we found that the release of dopamine and acetylcholine under stress is reduced in animals housed in an enriched environment. We also reported that the stress-induced release of dopamine but not acetylcholine is lower in aged rats compared with young rats. These results suggest that environmental enrichment reduces the reactivity to stress of the prefrontal dopaminergic and cholinergic systems in the rat. We further hypothesize that the positive effects on stress coping behaviors of housing animals in an enriched environment are associated with reductions, rather than increases, in the release of dopamine and acetylcholine in the prefrontal cortex. Finally we propose that a reduction in the stress-induced release of dopamine observed during aging in control animals might be an index of a better adaptation to stressful stimuli.

The prefrontal cortex (PFC) efferent projections to limbic areas facilitate a top-down control on the execution of goal-directed behaviours. The PFC sends glutamatergic outputs to limbic areas such as the hippocampus and amygdala which in turn modulate the activity of the nucleus accumbens (NAc). Dopamine and acetylcholine neurons in the brainstem and basal forebrain/septal areas, which send outputs to NAc, hippocampus and amygdala, are also regulated by PFC glutamatergic projections, and seem to be of special relevance in modulating motor, emotional and mnemonic functions. Both the physiological and pathological changes in the PFC influence the activity of these limbic areas and the corresponding final-guided behaviours. We revise our most recent studies on PFC-NAc interactions focussed on the role of dopamine and glutamate receptors in the PFC. Specifically, by performing microinjections/microdialysis studies we found that the activation of D2 dopamine receptors and the blockade of glutamate NMDA receptors in the PFC change the release of dopamine and acetylcholine in the NAc. We suggest the possibility that dopamine and glutamate receptors in the PFC could change the activity of dopamine and acetylcholine function in the hippocampus and amygdala. Finally, it is speculated that changes in the function of the PFC, associated with psychiatric disorders or due to environmental-dependent plasticity, can change PFC-limbic system interactions.

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