Ascending and descending projections from the median and dorsal raphe nuclei of the midbrain were mapped in the albino rat, using reduced-silver stains after lesions or the autoradiographic technique following injections of tritiated proline. In all major respects the two techniques gave the same results. The majority of the ascending projections sweep ventrally from the raphe nuclei, then curve rostrally to course through the ventral tegmentum and into the medial forebrain bundle (MFB). Others radiate through the mesencephalic reticular formation (RF) and central grey, turning ventrally at the posterior thalamic border to enter the subthalamus. From the MFB, fibers branch into the hypothalamus, preoptic areas, anterior amygdala and olfactory tubercle, while some fibers enter the fornix or the stria terminalis. Many fibers continue rostrally in the MFB, joining the diagonal bands of Broca to reach the septal nuclei or, further rostrally, the cingulum bundle. Fibers in the cingulum bundle turn caudally around the genu of the corpus callosum, some branching into the cell-free layers of the pregenual cortex. Runing caudally, then curving around the splenium, the cingulum bundle projection sprays out into the subiculum and in some cases a projection into the hippocampus is seen.

Other ascending projections include one to the habenular nuclei through the fasciculus retroflexus. Projections to the mediodorsal, parafascicular and reuniens nuclei of the thalamus were also noted.

Descending projections were observed to the dorsal tegmental nucleus and locus coeruleus and diffusely to the pontine reticular formation and caudal central grey. No projections were seen below the level of the facial nerve nucleus and none were observed to the cerebellum, caudal raphe nuclei or cranial nerve nuclei.

Connections of the median and dorsal raphe nuclei in the rat: an autoradiographic and degeneration study.

Physiopharmacological interactions between stress hormones and central serotonergic systems

Roles of steroid hormones and their receptors in structural organization in the nervous system

• The serum cortisol concentration following administration of 5-hydroxytryptophan (5-HTP), 200 mg orally, a precursor of serotonin (5-HT), was significantly greater in unmedicated depressed and manic patients than in normal controls. Increases in serum cortisol levels greater than 5 ug/dL were significantly more frequent in both unmedicated depressed and manic patients than in the normal controls. There was significant test-retest reliability. Baseline serum cortisol concentration correlated negatively with the cortisol response to 5-HTP in normal controls. These results suggest increased 5-HT receptor sensitivity may be present, possibly in the hypothalamus or pituitary, in some patients with affective disorders. These results are consistent with the hypothesis that decreased serotonergic activity, which would be expected to produce increased 5-HT receptor sensitivity, may be present in both depression and mania.

https://jamanetwork.com/journals/PSYCH/articlepdf/493312/archpsyc_41_4_009.pdf

Effect of 5-Hydroxytryptophan on Serum Cortisol Levels in Major Affective Disorders: I. Enhanced Response in Depression and Mania

Background. Depressed patients show deficits on neuropsychological tests. However, the basis of these impairments and their relationship with mood disturbance remains unclear. Methods. This paper reviews the literature regarding the relationship between mood disturbance and neuropsychological impairment in depression and the evidence for serotonergic and hypothalamic‐pituitary‐adrenal (HPA) axis involvement in these two domains. Results. Mood disturbance and neuropsychological impairment both occur in depression, but have no clear relationship in time or degree. Impairment of post-synaptic 5-HT "A receptor function may result in the symptom of low mood in depression. Depressed patients demonstrate abnormalities in the functional control of the HPA axis with a resultant hypercortisolaemia, which may impair neuropsychological function. These processes may be related given the extensive interactions between the serotonergic system and the HPA axis. Conclusions. We argue that there is a neurobiological cause of impaired neuropsychological function in depression. The complex relationship between neuropsychological function and mood may be a result of interactions between the serotonergic system and the HPA axis, particularly in the hippocampus with involvement of serotonergic 5-HT "A and glucocorticoid receptors. A primary dysfunction in these receptors will produce a lowering of mood and neuropsychological impairment respectively. Either dysfunction will result in a secondary impairment of the alternate system. Thus, the aective and psychological changes of depressive illness are likely to have complex relationships in time and severity to one another and the illness as a whole may result from a range of primary aetio-pathologies.

/pdf/mood-and-neuropsychological-function-in-depression-the-role-4f8uxbaizs.pdf

Mood and neuropsychological function in depression: the role of corticosteroids and serotonin

Rats were adrenalectomized 10 days before we estimated in vivo the conversion index of 3H-tryptophan into radioactive serotonin in brainstem and telediencephalon. We found that the conversion index in the brainstem of adrenalectomized rats is smaller than in the same area of sham-operated rats. Conversely, the conversion index in the telediencephalon was similar in the two groups of rats. The serotonin concentrations were unchanged by adrenalectomy, which suggests that in brainstem the decrease of tryptophan hydroxylase is reflected by the conversion index estimation and not by measurement of serotonin steady-state concentrations.

E. Costa

Papers

In vivo Conversion of 3H-L-Tryptophan into 3H-Serotonin in Brain Areas of Adrenalectomized Rats