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5-hydroxytryptamine at a concentration of 0.04 microgram/ml was able to block the ACTH release caused by hypothalamic tissue (CRF) while it was ineffective when a hypothalamic extract containing CRF was used. 5-hydroxytryptophan added to rat adrenal tissue caused a dose-dependent increase in corticosterone production. In a dose of 0.04 microgram/ml, 0.4 microgram/ml and 4.0 microgram/ml, 5-hydroxytryptophan was able to inhibit the ACTH release caused by hypothalamic tissue in vitro. However 0.04 microgram/ml was ineffective on the increase in ACTH secretion elicited by hypothalamic extract CRF. The data suggest that the inhibitory action of 5-hydroxytryptophan and 5-hydroxytryptamine is exerted at the hypothalamic level by inhibiting the release and/or synthesis of the corticotrophic releasing factor.

The effect of different doses of intracerebro-ventricularly administered cholecystokinin octapeptide sulphate ester (CCK-8-SE) was studied on dopamine (DA), norepinephrine (NE) and serotonin (5-HT) contents in the hypothalamus, mesencephalon, amygdala, septum and striatum, 10, 20 and 60 min following administration. The DA and NE content increased and the 5-HT content decreased in the hypothalamus and mesencephalon. A biphasic action was observed in the amygdala of DA, NE and 5-HT depending upon the time and doses used. Similar action was seen on DA and NE in the septum. In the striatum, the DA and 5-HT content decreased while the NE level first increased and then decreased. The data indicate that the CCK-8-SE is able to modify the activity of DA, NE and 5-HT in different brain regions in a time and dose-dependent manner, with a local specific action.

The effects of H-Phe-Ile-Tyr-His-Ser-Tyr-Lys-OH, a hypothalamic heptapeptide with weak CRF activity were investigated on the in vitro uptake and release of radiolabelled dopamine (DA), noradrenaline (NA) and serotonin (5-HT) in rat brain hypothalamic slices. In a doses of 5 X 10(-6) M and 10(-5) M the heptapeptide significantly increased the 5-HT uptake, whereas it had no effect on the DA and NA uptakes. The same doses (5 X 10(-6) M, 10(-5) M) significantly increased the DA release without affecting the NA and 5-HT release. These results suggest that H-Phe-Ile-Tyr-His-Ser-Tyr-Lys-OH as a hypothalamic peptide is able to modulate selectively the activity of the serotonergic and dopaminergic transmission without influencing the noradrenergic system in the hypothalamus.

The effect of lysine-8-vasopressin (LVP) and oxytocin (OXT) has been studied on the steady-state level of serotonin (5-HT),dopamine(DA) and norepinephrine (NE) in various brain areas four hours after intraventricular microinjection of the neuropeptides. LVP (50 microU) diminished in content of 5-HT and NE in the mesencephalon, the content of 5-HT in the septum as well as the content of DA and NE in the dorsal hippocampus. OXT (500 microU), on the other hand, decreased the content of 5-HT, DA and Ne in the hypothalamus, as well as the content of DA in the mesencephalon. In contrast, the septal NW level was increased following OXT treatment. The data indicate that both LVP and OXT are capable of influencing the 5-HT and catecholamine levels as late as 4 h after their administration. Therefore, our findings support the previous notion that posterior pituitary neuropeptides affect behavioral processes via interacting with the cerebral monoaminergic neurotransmission.

Pargyline-induced accumulation of serotonin (5-HT) was used as an index of 5-HT turnover rate in the dorsal hippocampus. One hour after bilateral removal of the adrenals, 5-HT turnover was significantly reduced when compared to that of the sham-operated controls. A low dose of corticosterone given immediately after adrenalectomy restored the 5-HT response, while the same dose of dexamethasone was ineffective. Pretreatment with dexamethasone blocked the 5-HT response to corticosterone in the acutely adrenalectomized rat. The specificity of the 5-HT response in the hippocampus corresponds to the properties of the glucocorticoid receptor system in rat hippocampal neurons.

The effects of intracerebroventricular administration of cholecystokinin (CCK) antiserum )specific for COOH-terminal four amino acids) of CCK were tested in three dilutions on the dopamine (DA), norepinephrine (NE) and serotonin (5-HT) contents of the hypothalamus, amygdala, septum, striatum and cerebral cortex in rats 24 h following application. CCK antiserum decreased the DA and NE contents in the hypothalamus, mesencephalon, amygdala and septum, while it increased the DA content and decreased the NE content of the striatum. It had a slight effect on the 5-HT contents of the amygdala, septum and striatum.

Compared to heterozygous Brattleboro animals, homozygous (diabetes insipidus) rats exhibited higher steady-state levels of serotonin in the mesencephalon, septum and striatum. These differences disappeared upon the administration of pargyline, suggesting accumulation of serotonin. The norepinephrine level was higher in the mesencephalon, while the disappearance rate (alpha-met hyl-p-tyrosine) was accelerated in the septum and decreased in the hypothalamus. The lower striatal dopamine level was associated with a decreased disappearance rate. The data suggest that the altered monoamine metabolism might be associated with the known endocrine and behavioral disturbances of the homozygous rats.

Fifteen min after ether stress, the 5-hydroxytryptamine (5-HT) content of the rat hypothalamus decreased, while after electric shock no decline was noted in the mesencephalon and the hypothalamus. At 30 min an increase occurred in the mesencephalon and amygdala and at 60 min in the hypothalamus after both stressors. Fifteen min after electric shock the 5-hydroxyindoleacetic acid (5-HIAA) content was increased in the amygdala, while after both stressors in the mesencephalon and hypothalamus 30 min and after ether stress in the amygdala. In the hippocampus and the septum the 5-HT or 5-HIIA content was unaffected by either type of stress. 5-HT turnover decreased between 10 and 20 min after ether stress in the hypothalamus and after electric shock in the mesencephalon and hypothalamus. Between 50 and 60 min after electric shock, 5-HT turnover increased in the mesencephalon. Other brain areas showed no significant difference from the control 5-HT value. 3H-5-HT uptake decreased in the mesencephalon and hypothalamus 20 min after ether stress, but returned to normal after 60 min. The plasma corticosterone level was highest at 30 min after both stressors and returned to normal 90 min after stress. Therefore, the stress-induced decrease of serotoninergic activity in certain limbic brain structures, especially in the hypothalamus, suggests an inverse relationship with pituitary-adrenal activity. This finding would further support the concept that the serotoninergic system plays an inhibitory role in pituitary-adrenal function.

A single dose of corticosterone (1 mg/kg b.w.i.p.) increased the 5-hydroxytryptamine (5-HT) content in the mesencephalon, amygdala and hypothalamus. The maximum was observed at 15 min following administration. The 5-HT level returned to normal between 60 and 180 min. The 5-hydroxyindoleacetic acid (5-HIAA) content decreased in the mesencephalon and hypothalamus at 15 min, and then increased to the maximum at 30 min in the mesencephalon and at 45 min in the hypothalamus and amygdala. There were no changes in the septum and hippocampus either in 5-HT or in 5-HIAA content following corticosterone administration. Desoxycorticosterone administration (1 mg/rat i.p.) was ineffective. Tritiated 5-HT uptake did not change in the hypothalamus and mesencephalon tissue in vitro after corticosterone or desoxycorticosterone treatment. Adrenalectomy caused a decrease in the 5-HT content in all brain areas studies. 5-HIAA decreased only in the hypothalamus. Corticosterone administration normalized the 5-HT and 5-HIAA content in the hypothalamus and mesencephalon in adrenalectomized rats. Tritiated 5-HT uptake was lower in the hypothalamus and mesencephalon in adrenalectomized rats. Corticosterone administration increased the activity back to normal in the hypothalamus, however desoxycorticosterone was ineffective. The data suggest that the plasma corticosterone level plays a role in the regulation of the activity of the serotoninergic system in certain limbic brain structures.

The effects of graded amounts of centrally injected [intracerebroventricular, i.c.v.] oxytocin [OXT] have been studied on the steady-state level and pargyline-induced accumulation of serotonin [5-HT] in the hypothalamus, mesencephalon and dorsal hippocampus of rats. OXT only weakly affected the steady-state level of 5-HT. The pargyline-induced accumulation, on the other hand, was inhibited by central OXT treatment. Whereas OXT inhibited 5-HT accumulation in a dose-dependent manner in the hypothalamus, only the lowest amount of OXT was effective in the mesencephalon and the dorsal hippocampus. The data raise the possibility that an altered 5-HT metabolism is likely to have functional significance in the endocrine and behavioral effects of OXT.

Prolyl-leucyl-glycinamide (PLG) and its substituted and protected analogues were tested on the steady-state level of noradrenaline (NA), dopamine (DA) and serotonin (5-HT) in various brain areas. The tripeptides were structurally modified at the N-terminal proline residue either by protection with benzoxycarbonyl (Z group) or by tertiary butyroxycarbonyl (BOC), or by substitution with homoproline (HPRO). C-terminal modification was performed by substitution of the amino group of glycine (GLY-NH2) by methylester (GLY-OMe). The parent molecule (PLG) increased the 5-HT content in the striatum and the NA and DA levels in the dorsal hippocampus. N-terminal protection by Z-group resulted in a loss of these effects. Striatal effects re-appeared if a methylester group was introduced in the C-terminal glycine. Substitution of the N-terminal with HPRO or that of the C-terminal amine group by OMe resulted in a tendency to increase the 5-HT level in the hypothalamus.

The effect of modified and substituted analogues of prolyl-leucyl-glycinamide (PLG, MIF-I) was investigated on the steady-state level of noradrenaline (NA), dopamine (DA) and serotonin (5-HT) in various brain regions. Proline was replaced by D- or L-pipecolic acid (D- or L-Pip), which analogues in turn were protected by benzoxy-carbonyl (Z) group. Substitution by D- or L-pipecolic acid caused opposite changes in the DA level of the dorsal hippocampus. These effects were absent it the N-terminal of either analogues was protected by Z-group. Following the above mentioned N-terminal modification, the amino group of the C-terminal glycine was also substituted by methyl-esther (Gly-OMe), Z-D-Pip-Leu-Gly-OMe decreased the mesencephalic DA level, while Z-L-Pip-Leu-Gly-OMe increased the 5-HT content of the mesencephalon and striatum. In general, N-terminal substitution by D-pipecolic acid decreased, whereas that by L-pipecolic acid increased the monoamine level in the brain.

A modification of previously published fluorimetric methods for brain noradrenaline (NA), dopamine (DA), and serotonin (5-HT) assay is presented in this paper. The modification improved the sensitivity to 5-HT and resulted in a less time-consuming and less expensive method for noradrenaline and dopamine determination. The assay can be used for simultaneous estimation of NA, DA and 5-HT as well as for turnover studies, utilizing catecholamine synthesis inhibition or monoaminoxidase inhibition.

The effect of glutaurine (gamma-L-glutamyl-taurine, Litoralon) was studied on dopamine, norepinephrine and serotonin turnover in the hypothalamus, mesencephalon, amygdala, septum, hippocampus, cortex and cerebellum following intracerebroventricular administration. Dopamine and norepinephrine turnover, measured by alpha-methyl-paratyrosine inhibition of catecholamine synthesis, increased in the cerebellum and the norepinephrine turnover in the hypothalamus. Serotonin turnover, measured by serotonin accumulation induced by the MAO inhibitor pargyline, decreased in the mesencephalon. There was no change in catecholamine or serotonin turnover in the amygdala, septum, hippocampus and cortex. The data suggested a highly selective action of glutaurine on brain transmitters in certain brain areas, especially in the cerebellum.

The effect of corticosterone administered in different doses has been studied on hypothalamic serotonin (5-HT) content. A single intraperitoneal injection of the hormone in doses of 1.0 and 2.0 mg/kg bw. increased the serotonin content of the hypothalamus at 30 min after administration. Five mg/kg had no effect, while 10.0 mg/kg decreased the serotonin content. The data provide an explanation for the controversial findings of different authors having used different doses of different glucocorticoids and on the basis of the results it is emphasized that the action of glucocorticoids on hypothalamic 5-HT content is a dose-dependent dual effect.

The influence of lysine-8-vasopressin (LVP) on the steady-state level of serotonin was studied in different brain regions four hours after microinjection into the lateral ventricle (icv) or cisterna magna (cm). LVP (200 pg) increased the serotonin (5-HT) level in the hypothalamus and mesencephalon after cm application, while icv administration caused an opposite tendency. The findings suggest that the site of peptide administration is of decisive importance in the mediation of various effects of LVP on the transmitter metabolism. A possible link exists between opposite effects of cm versus icv injection of LVP on central serotoninergic mechanisms, as well as on behavioral and autonomic correlates of these treatment.