In Search of Concomitant Alterations of Dopaminergic and Neurotensinergic Systems in Stress Conditions

The aim of the present article is to review experimental evidence which suggest joint involvement of both the dopaminergic and neurotensinergic systems in stress conditions. At present, the concept of stress refers to an environmental demand exceeding the normal regulatory ability of an organism, particularly during unpredictable and uncontrollable situations. Chronic stress yields devastating effects including cognitive and working memory dysfunctions, for which neurotransmission mediated by the catecholamines dopamine and noradrenaline is crucial. Catecholamine synthesis depends on the rate-limiting enzyme, tyrosine hydroxylase, whose expression is associated with working memory and the response to chronic stress. Neurotensin is a tridecapeptide widely distributed in the nervous system, at both central and peripheral levels, which behaves as a neurotransmitter or neuromodulator. It mediates diverse biological actions including reward, locomotion, pain modulation and stress. Neurotensin and its high affinity NTS1 receptor are densely localized in areas that process emotion (amygdala nucleus), cognition (such as hippocampal nuclei and cortical areas) and the response to stress (hypothalamic nucleus). Experimental evidence indicates a crosstalk between the dopaminergic and the neurotensinergic systems either from an anatomical or a biochemical point of view. It is suggested that a concomitant alteration of dopaminergic and neurotensinergic systems takes place in diverse stress conditions.