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Mammillary bodies are relay nuclei within limbic and extralimbic connections. Whereas other subcortical brain structures have been found to be altered in depression, no current information exists regarding the pathomorphology of mammillary bodies in affective disorders. We studied the postmortem brains of 19 human subjects with mood disorders (9 with major depressive disorder and 10 with bipolar I disorder) and 20 control individuals and assessed the mammillary body and fornix volumes, number of neurons and neuronal densities. We found that male control subjects have significantly larger mammillary bodies compared with females. In addition, control subjects of both sexes with the diagnosis/cause of death of "heart failure/insufficiency" had significantly smaller mammillary body volumes compared with non-psychiatric patients who died from other causes. When estimating the mammillary bodies volumes of patients with depression compared with control subjects, a significant reduction of the left mammillary body volume was found in patients with bipolar disorder, but not in patients with major depression. However, significant depression-associated mammillary body volume reductions were found between the control subjects who did not die of heart failure and patients with major depression and bipolar disorder. Moreover, the MB volumes of control subjects who died of heart failure were in the range exhibited by subjects with depression. There was no significant influence of suicidal behavior on mammillary volumes observed. Moreover, no significant group differences in the total neuronal number or neuronal density were found between the controls, subjects with major depression and subjects with bipolar disorder. Furthermore, the fornix volumes were significantly reduced only in the control subjects with heart failure. Taken together, these results show that the mammillary bodies are compromised in depression.

We have studied the effects of nociceptin/orphanin FQ on the histaminergic neurons in the tuberomammillary (TM) nucleus and compared them with the actions of opioid agonists. Intracellular recordings of the membrane potential were made with sharp electrodes from superfused rat hypothalamic slices. Nociceptin strongly inhibited the firing of the TM neurons. In the concentration range 10-300 nM, nociceptin hyperpolarized the neurons in a dose-dependent and reversible manner. Insensitivity to tetrodotoxin indicated a postsynaptic effect which was associated with decreased input resistance. Voltage-current plots suggested the involvement of a potassium conductance which was highly sensitive to Ba(2+) and decreased by Cs(+), in keeping with the activation of an inwardly rectifying potassium channel. Morphine (20-100 microM) depolarized the TM neurons and increased their firing, and this effect was blocked by tetrodotoxin. Dynorphin A(1-13) at 100-300 nM did not affect the TM neurons. Nociceptin and morphine modulate the activity of the TM neurons, and most likely histamine release, in opposite ways. Histamine has an antinociceptive effect in the brain and may be involved in opioid-induced analgesia. Nociceptin might therefore influence pain transmission by inhibiting opioid-induced histamine release from the TM nucleus and also modulate other physiological mechanisms which have been ascribed to the histaminergic system.

The MAP kinase phosphatase 1 (MKP-1), a dual serine-threonine phosphatase, inactivates the MAP kinases ERK and JNK/SAPK which are involved in neuronal survival and neuronal cell death following injury and degenerative stimuli. We have studied by immunocytochemistry whether regulation of MKP-1 is part of the cell-body response following nerve fiber transection. The expression of MKP-1 was investigated in axotomized neurons of the corpus mamillaris (CMm) and substantia nigra pars compacta (SNC) following transection of the mamillo-thalamic tract (MT) and the medial forebrain bundle (MFB), respectively. In contrast to the surviving CMm neurons, the vast majority of SNC neurons undergoes cell death following axotomy. MKP-1 immunoreactivity which is absent in untreated adult rats, appeared in CMm neurons 24 h following MT transection, reached a maximum after 2 days and persisted in a substantial proportion of CMm neurons until 20 days, the end of observation period. In contradistinction, MKP-1 could not be detected in the SNC neurons. MKP-1 immunoreactivity was virtually restricted to the nuclei of neurons. Subcutaneous injection of the immunosuppressant FK506 that protects axotomized SNC neurons against neuronal cell death, enhanced the expression of MKP-1 in CMm, but failed to do so in SNC neurons. The selective expression of MKP-1 in CMm is the first finding on a different regulation of components in the stress kinase signal pathway in surviving vs. degenerating axotomized neurons., (Copyright 1998 Elsevier Science B.V.)