Effects of withdrawal from chronic exposure to cigarette smoke on hypothalamic and preoptic catecholamine nerve terminal systems and on the secretion of pituitary hormones in the male rat.

A 48 h but not a 72 h or 7 day withdrawal from chronic exposure to cigarette smoke was associated with increased noradrenaline levels (quantitative histofluorimetry) in the subependymal layer (SEL) of the median eminence, the anterior periventricular hypothalamic region (PV I) and the parvocellular part of the hypothalamic nucleus (PA FP) and an increased noradrenaline utilization (tyrosine hydroxylase inhibition by alpha MT) in the SEL and the PV I. Following a 48 h or 72 h but not a 7 day withdrawal from chronic exposure to cigarette smoke an increased catecholamine utilization was found in the medial palisade zone (MPZ) of the median eminence. Reduced serum prolactin, FSH and corticosterone levels were found following a 48 h withdrawal from chronic exposure to cigarette smoke. Following a 72 h withdrawal from chronic exposure to cigarette smoke a reduced concentration of serum prolactin was noted. Chronic exposure to cigarette smoke reduced serum TSH levels and lead to a tolerance development with regard to noradrenaline levels and utilization within the preoptic region with the exception of the periventricular preoptic region. The finding of special interest in the present study is the demonstration of a highly significant lowering of corticosterone serum levels despite maintained blood levels of ACTH as seen 48 h following withdrawal. It is suggested that this type of endocrine change may lead to changes in fear-motivated behaviour and contribute to behavioural withdrawal reactions. The maintained reductions of serum prolactin levels found after 48 h and 72 h of withdrawal from cigarette smoke exposure (cf. Andersson et al. 1985a) is discussed in terms of an increased catecholamine utilization in the medial palisade zone of the median eminance. This activation is suggested to be caused by the development of a prolactin receptor supersensitivity within the medium eminence. The present evidence indicates withdrawal effects mainly in the noradrenaline nerve terminals of the subependymal layer of the median eminence, the anterior periventricular hypothalamic region and the parvocellular part of the paraventricular hypothalamic nucleus which inter alia are involved in regulation of ACTH secretion (cf. Andersson et al. 1985a).

Effects of acute intermittent exposure to cigarette smoke on hypothalamic and preoptic catecholamine nerve terminal systems and on neuroendocrine function in the diestrous rat.

Diestrous female rats were exposed to the smoke from one to four cigarettes. Exposure to unfiltered cigarette smoke produced dose- and time-dependent reductions of catecholamine levels and dose- and time-dependent increase in catecholamine utilization in the various hypothalamic and preoptic dopamine and noradrenaline nerve terminal systems. These effects were counteracted by pretreatment with the ganglion blocking agent mecamylamine (1 mg/kg). Exposure to cigarette smoke was also found to produce a dose- and time-dependent inhibition of serum prolactin, LH and FSH levels which was counteracted by pretreatment with mecamylamine. Exposure to the smoke from one cigarette (but not from four cigarettes) increased serum TSH levels. In combination with tyrosine hydroxylase inhibition the exposure to cigarette smoke produced a dose- and time-dependent inhibition of plasma ACTH levels, an action which was counteracted by pretreatment with mecamylamine. The results demonstrated a sex difference (cf. Anderson et al. 1985c), in the nicotine-induced changes of TSH and ACTH secretion despite a general increase in hypothalamic and preoptic dopamine and noradrenaline utilization in both the male and the diestrous female rat. The differences in the neuroendocrine actions of acute intermittent exposure to cigarette smoke in the diestrous rat and the normal male rat are discussed.

Effects of intraventricular injections of galanin on neuroendocrine functions in the male rat. Possible involvement of hypothalamic catecholamine neuronal systems.

Galanin-catecholamine interactions have been analysed within the hypothalamus and the anteromedial frontal cortex of male rats by means of quantitative histofluorimetrical and biochemical measurements of catecholamine fluorescence in discrete catecholamine nerve terminal systems and measurements of serum levels of adenohypophyseal hormones and corticosterone using radio-immunoassay determinations. 125I-galanin binding sites were analysed and related to the distribution of galanin-immunoreactive neuronal structures in the median eminence and paraventricular hypothalamic nucleus. The results show that intraventricular injections of galanin in the awake and unrestrained male rat produce rapid increases of prolactin and growth hormone secretion but no effects on serum luteinizing hormone, thyroid stimulating hormone or on corticosterone levels. These changes in neuroendocrine function were associated with a selective reduction of the catecholamine stores in the medial palisade zone of the median eminence at the 20 min time interval. 125I-galanin binding sites were found throughout the hypothalamus including the median eminence and the magnocellular part of the paraventricular hypothalamic nucleus with a good correspondence with galanin immuno-reactivity. It is suggested that the enhancement of prolactin secretion induced by galanin involves an interaction between galanin and dopamine in the medial palisade zone leading to a reduced synthesis and/or release of dopamine and thus to a reduced prolactin inhibitory activity and to increases in prolactin secretion. A possible involvement of hypothalamic catecholamines in the galanin-induced changes of growth hormone secretion remains to be established.

Effects of acute continuous exposure of the rat to cigarette smoke on amine levels and utilization in discrete hypothalamic catecholamine nerve terminal systems and on neuroendocrine function.

The effects of acute continuous exposure to the smoke from 1-4 cigarettes have been studied in the male rat in terms of hypothalamic catecholamine levels and utilization as well as the secretion of anterior pituitary hormones. Catecholamine levels in discrete hypothalamic catecholamine nerve terminal systems were studied by quantitative histofluorimetry. Catecholamine utilization was studied by means of the tyrosine hydroxylase inhibition method using alpha-methyl-(+/-)-p-tyrosine methyl ester. The serum hormone levels of adenohypophyseal hormones and of corticosterone were measured by the use of radioimmunoassay procedures. The results show that acute continuous exposure to unfiltered but not to filtered (Cambridge glass fibre filters) cigarette smoke leads to small but dose-dependent reductions of amine levels in most of the hypothalamic noradrenaline and dopamine nerve terminal system. These effects were associated with an enhancement of regional hypothalamic noradrenaline utilization but not of dopamine utilization in the median eminence. Furthermore, a reduction of TSH and prolactin serum levels was noted as well as increases in ACTH secretion. These results are partly different from those previously obtained with rats acutely exposed to intermittent unfiltered cigarette smoke. This difference is suggested to be due to a temporary blockade of catecholamine release following acute continuous exposure to cigarette smoke.

Further studies on the effects of central administration of neuropeptide Y on neuroendocrine function in the male rat: relationship to hypothalamic catecholamines.

Following intraventricular (i.v.t.) administration of increasing doses of neuropeptide Y (NPY; 7.5-750 pmol/rat) the catecholamine levels and turnover were quantitatively measured in discrete hypothalamic regions by means of histofluorometry. In the same rats the adenohypophyseal hormones as well as vasopressin, aldosterone (ALDO) and corticosterone (CORTICO) levels in serum were determined. Neuropeptide Y seems to induce a biphasic change in amine utilization in the tuberoinfundibular dopamine (DA) neurons and in the noradrenergic (NA) utilization in various hypothalamic areas. Thus, the lowest doses seem to inhibit the catecholamine utilization while higher doses seem to enhance it. NPY (250-750 pmol) reduced the serum levels of thyreotropine (TSH), prolactin (PRL) and growth hormone (GH) but increased CORTICO, adrenocorticotropin (ACTH) and ALDO serum levels. In conclusion, it is suggested that the NPY induced changes in DA utilization in the tuberoinfundibular DA neurons may contribute to the NPY induced changes in PRL and TSH secretion. The increases in paraventricular NA utilization may contribute to the increases in ACTH, ALDO and CORTICO secretion induced by NPY. These data give further support for NPY as an important neuroendocrine modulator.

Nicotine-induced increases in brain luteinizing hormone releasing hormone-like immunoreactivity and in serum luteinizing hormone levels of the male rat.

By means of radioimmunoassay procedures luteinizing hormone releasing hormone (LHRH)-, Metenkephalin- and somatostatin-like immunoreactivities have been measured in discrete hypothalamic and preoptic nuclei as well as serum luteinizing hormone (LH) levels. Nicotine (2 mg/kg, i.p.) produced after 5 min a significant and selective increase in LHRH-like immunoreactivity in the median eminence and in the medial preoptic nucleus, associated with increases in serum LH levels but without any changes in Met-enkephalin and somatostatin-like immunoreactivities in the median eminence. The results indicate that the nicotine-induced activation of LHRH-immunoreactive neurons involves an enhanced processing of the precursor peptide to LHRH.

Mapping of glucocorticoid receptor immunoreactive neurons in the rat tel- and diencephalon using a monoclonal antibody against rat liver glucocorticoid receptor.

By means of a monoclonal antibody against the rat liver glucocorticoid receptor (GR) in combination with the indirect immunoperoxidase technique it has been possible to demonstrate GR-immunoreactive nerve and glial cell nuclei all over the tel- and diencephalon of the male rat. Strongly GR-immunoreactive nerve cell nuclei were only present in the parvocellular part of the paraventricular hypothalamic nucleus, in the anterior periventricular hypothalamic nucleus, in the ventral part of the mediobasal hypothalamus, and in the CA1 and CA2 subregion of the hippocampal formation. Within the paraventricular hypothalamic nucleus a substantial overlap exists between the GR-immunoreactive area and the CRF-immunoreactive area. Medium to high densities of moderately GR-immunoreactive nerve cell nuclei were present all over the cortical hemispheres. Medium densities of moderately GR-immunoreactive nerve cells were demonstrated in many thalamic nuclei and in the central amygdaloid nucleus. After adrenalectomy the GR immunoreactivity was predominantly located in the pericaryon. Upon acute corticosterone treatment of adrenalectomized male rats, the GR immunoreactivity was again mainly demonstrated in the nerve cell nuclei indicating that corticosterone can translocate GR from the cytoplasm to the cell nuclei. It is suggested that the hypothalamic GR may be involved in the regulation of especially CRF secretion but also in the secretion of other anterior pituitary hormones such as TRH and somatostatin.

Cholecystokinin neuron systems and their interactions with the presynaptic features of the dopamine neuron systems. A morphometric and neurochemical analysis involving studies on the action of cholecystokinin-8 and cholecystokinin-58.

A unique role for CCK-58 compared to that for CCK-8 has been demonstrated in the modulation of central catecholaminergic mechanisms and neuroendocrine functions. It is of paramount importance to localize CCK-58 immunoreactivity within the brain in order to establish if separate CCK-58- and CCK-8-immunoreactive neuron systems exist. The two most significant actions of CCK-58 are a marked lowering of TSH secretion and a selective increase of DA turnover in DA-CCK co-existing synapses in the nucleus accumbens and tuberculum olfactorium.

Distribution of neurophysin II immunoreactive nerve fibers within the subnuclei of the nucleus of the tractus solitarius of the rat.

The location of neurophysin II immunoreactive nerve fibers and preterminal processes has been examined in various functionally distinct subnuclei of the nucleus of the tractus solitarius (nTS) using the indirect immunofluorescence method for immunocytochemistry combined with cytoarchitectonic identification. The nTS is responsible for integrating respiratory and autonomic reflex activity: the vlnTS, vnTS, ni and nI are associated with respiratory activity; the dlnTS and dnTS are important sites for the integration of baroreceptor and chemoreceptor activity; the ncom, dnTS and dlnTS integrate cardiac afferent activity and the mnTS mediates both cardiovascular and gastrointestinal effects. At levels caudal to the obex, the ncom contained the largest number of neurophysin II immunoreactive nerve fibers and the mnTS and dmnX contained moderate neurophysin II immunoreactivity. At levels rostral to the obex the region of the dorsal medulla adjacent to the mnTS and dnTS (PVR and dPSR) showed the densest immunoreactivity and the mnTS, dmnX and vPSR showed moderate immunoreactivity. At the rostral pole of the nTS, neurophysin II immunoreactive nerve terminals were seen in the dendritic regions of cells in dmnX and mnTS. This selective distribution of neurophysin II immunoreactive nerve terminals in the cardiovascular and gastrointestinal subnuclei of the nTS implicates a direct, descending, hypothalamic, oxytocin-neurophysin II containing pathway interacting with these nTS functions. These results confirm the hypothesis (Sawchenko and Swanson) that descending neurophysin II immunoreactive pathways represent an important neuronal system for the hypothalamic regulation of cardiovascular (vasomotor) and gastrointestinal nuclei in the brainstem.

Selective reduction of adrenaline turnover in the dorsal midline area of the caudal medulla oblongata and increase of hypothalamic adrenaline levels in the Lyon strain of genetically hypertensive rats.

Catecholamine levels and turnover have been studied in 5 week old male genetically hypertensive (LH) and normotensive (LN) rats of the Sprague-Dawley Lyon strain. The results demonstrate increased hypothalamic adrenaline levels and a reduced adrenaline turnover in the dorsal midline of the medulla oblongata (DCMO) in the LH rats compared with LN control rats. The reduction of adrenaline turnover in the DCMO may contribute to the development of spontaneous hypertension.

Acute sino-aortic denervation in rats produces a selective increase of adrenaline turnover in the dorsal midline area of the caudal medulla oblongata and a reduction of adrenaline levels in the anterior and posterior hypothalamus.

Acute sino-aortic denervation produces an acute reduction of adrenaline stores in the anterior and posterior hypothalamus and a reduction of noradrenaline stores in the dorsal midline area of the caudal medulla oblongata. Furthermore, removal of baroreflex afferents results in an increase of adrenaline turnover in the DCMO but not in the hypothalamus. The present findings give evidence for participation of adrenergic mechanisms in central baroreflex regulation. The findings can be interpreted according to the adrenaline vasodepressor hypothesis of hypertension.