Studies on neuropeptide Y-catecholamine interactions in the hypothalamus and in the forebrain of the male rat. Relationship to neuroendocrine function.

Neuropeptide Y-catecholamine interactions have been analyzed within the hypothalamus and in the forebrain of male rats by means of immunocytochemistry in combination with morphometry, quantitative histofluorimetry on catecholamine fluorescence in discrete catecholamine nerve terminal systems, biochemical analysis of catecholamines as well as by studies on serum levels of adenohypophyseal hormones vasopressin, adrenocortical hormones and angiotensin II using radioimmunoassay determinations. (1) Morphologic and morphometrical evidence indicates the existence of separate populations of neuropeptide Y and tyrosine hydroxylase immunoreactive nerve cell bodies in the parvo- and magnocellular components of the arcuate nucleus respectively. In addition, a significant codistribution of NPY immunoreactive nerve terminals and tyrosine hydroxylase immunoreactive nerve cell bodies were demonstrated in the ventrolateral part of the magnocellular component of the arcuate nucleus. (2) Immunocytochemical studies on the distribution of tyrosine hydroxylase, phenyl ethanolamine-N-methyltransferase and neuropeptide Y immunoreactive nerve terminal networks in the peri- and paraventricular hypothalamic nucleus indicated that these types of immunoreactive nerve terminals densely innervate the medial and anterior parvocellular part of the paraventricular hypothalamic nucleus and anterior periventricular hypothalamic nucleus. From studies on the pattern of terminal distribution results have been obtained compatible with the view that neuropeptide Y or a neuropeptide Y related peptide can be a comodulator in noradrenaline and adrenaline nerve terminal networks of these regions. (3) Acute intraventricular injections of neuropeptide Y (1.25 nmol) do not change dopamine and noradrenaline levels in any hypothalamic and telencephalic dopamine and noradrenaline nerve terminal system analyzed with the exception of the anteromedial frontal cortex, in which area a significant increase in the dopamine levels was observed as revealed biochemically. (4) By means of the tyrosine hydroxylase inhibition method it was possible to show that acute intraventricular injection of NPY (1.25 nmol) increased dopamine utilization in the medial and lateral palisade zone of the median eminence and in the anteromedial frontal cortex and reduced noradrenaline utilization in the parvocellular part of the paraventricular hypothalamic nucleus, while dopamine utilization was not influenced in the nucleus caudatus putamen, nucleus accumbens or in the tuberculum olfactorium. (5) In the intraventricular experiments reported above neuropeptide Y (1.25 nmol, 1 h) reduced the serum levels of thyreotropin stimulating hormone, prolactin and luteinizing hormone and increased serum corticosterone, adrenocorticotrophin, vasopressin, angiotensin II and aldosterone levels. The presence of the tyrosine hydroxylase inhibitor by itself, increased corticosterone, adrenocorticotrophin and aldosterone serum levels and reduced serum luteinizing hormone levels. Neuropeptide Y together with the tyrosine hydroxylase inhibitor further enhanced the adrenocorticotrophin, angiotensin II and aldosterone serum levels seen with the inhibitor, but could no longer produce its excitatory and inhibitory effects on serum corticosterone and luteinizing hormone levels, respectively. Vasopressin serum levels were increased to the same extent in the absence or presence of tyrosine hydroxylase inhibition. The present morphological, neurochemical and functional studies indicate that neuropeptide Y given intraventricularly inhibit the secretion of prolactin, luteinizing and thyreotropin stimulating hormones probably by activation mainly of neuropeptide Y receptors located in the somadendritic region of the arcuate DA cell bodies, leading to increased activity in inhibitory tubero-infundibular dopamine neurons. In addition, it is suggested that the ability of neuropeptide Y to increase adrenocorticotrophin and corticosterone secretion is at least in part related to its ability to reduce noradrenaline turnover in the parvocellular part of the paraventricular hypothalamic nucleus, rich in corticotrophin releasing factor immunoreactive nerve cell bodies. It is speculated that neuropeptide Y as a comodulator in the noradrenaline nerve terminals in this area may enhance the excitatory actions of noradrenaline on the corticotrophin releasing factor immunoreactive nerve cells. Such an action will lead to increases of corticotrophin releasing factor neuronal activity and of adrenocorticotrophin hormone secretion producing a feedback response, which may reduce noradrenaline turnover exclusively in this nucleus as was observed in the present experiments. The increase in aldosterone may be induced by the increased adrenocorticotrophin serum levels but the increase in vasopressin secretion and in angiotensin II serum levels may be secondary to the hypotensive activity of neuropeptide Y. Finally, it is suggested that neuropeptide Y mechanisms can increase dopamine synthesis and release in the anteromedial frontal cortex. Thus, neuropeptide Y mechanisms may participate in the control of cortical functions at least partly by regulating the cortical dopamine neurotransmission.