Met-enkephalin immunoreactive neurons recruited by acute stress are innervated by axon terminals immunopositive for tyrosine hydroxylase and dopamine-α-hydroxylase in the anterolateral division of bed nuclei of the stria terminalis in the rat

The bed nuclei of the stria terminalis (BST) are highly heterogeneous forebrain structures, which play a central role in the regulation/modulation of stress responses. Studies using the inducible immediate early gene c-fos as a marker of activated neurons have demonstrated significant stress-induced neuronal activation in this limbic region. The BST also exhibit a dense network of dopamine and noradrenaline immunoreactive (ir) axon terminals. These catecholaminergic projections from various brainstem sources to the BST play an important role in a neurochemically mediated coordination of stress responses. In the anterolateral division of bed nuclei of the stria terminalis, the distribution of several Met-enkephalin immunopositive perikarya overlaps with that of catecholaminergic axon terminals. Both monoaminergic and enkephalinergic structures have been postulated to play a role in the regulation/modulation of the central regulatory pathways of endocrine, behavioural and physiological responses during stress. Therefore the aims of this study were: (i) to study the possible involvement of dopaminergic fibre terminals in stress-induced activation of BST perikarya; (ii) to investigate whether Met-enkephalin-immunoreactive neurons are recruited by acute volumen/osmotic challenge; and (iii), to demonstrate synaptic interactions between Met-enkephalin-ir neurons and fibre terminals immunopositive for dopamine or noradrenaline in the anterolateral division of the BST. From the results of this study we can conclude that depletion of dopamine in fibre terminals completely abolished stress-induced activation of perikarya in the anterolateral division of BST. Furthermore, the innervation of stress-induced Met-enkephalin-ir perikarya by dopaminergic fibre terminals in the oval nucleus of BST was demonstrated, whereas noradrenergic axons contacted enkephalinergic structures in the fusiform and subcomissural nuclei of BST. These interactions can be central in the modulatory control of the major stress regulatory pathway, the limbic hypothalamo-pituitary-adrenal axis.