UTILIZING MOLECULAR BIOLOGICAL AND HISTOPATHOLOGICAL TECHNIQUES TO STUDY THE DOPAMINERGIC SYSTEM IN PATIENTS WITH MELANCHOLIA

Objective: To describe the rationale for investigating the dopaminergi c system in patients with melancholia by applying molecular biological (notably, in situ hybridisation) and histopathological techniques in postmortem brain tissue.Method: Relevant advances in the functional ne uroanatomy of frontostriatal circuits, as well as insights from clinic al neuroimaging studies in primary and secondary depressive disorders, are presented, These are integrated with developments in the pharmaco logical and molecular characteristics of dopamine receptor subtypes an d recognition of their selective anatomical distribution. Results: Con verging data from the basic and clinical neurosciences suggest that th e pathophysiology of depressive disorders characterised by psychomotor phenomena, such as melancholia, may involve dysregulation of dopamine rgic mechanisms within complex frontostriatal circuits. Conclusions: T he key feature of in situ hybridisation is its capacity to test for va riations in the functional components of designated biochemical system s within highly specific anatomical regions. We utilise this approach, in combination with relevant histopathological techniques, to test th e structural and functional integrity of the dopaminergic system withi n key fronto-striatal circuits in patients who had exhibited psychomot or phenomena, The same approach can also be used to study the integrit y of other relevant biochemical systems, such as the serotoninergic an d noradrenergic systems, in patients with other mood disorders.