Noradrenaline Nerve Terminal Systems Research Articles

Effects of Combined Pre‐ and Postnatal Treatment with Nicotine on Hypothalamic Catecholamine Nerve Terminal Systems and Neuroendocrine Function in the 4‐Week Old and Adult Male and Female Diestrous Rat

Abstract Male and female Sprague-Dawley rats were treated with nicotine during the prenatal period and the first three postnatal weeks (the pregnant and lactating rats were given nicotine hydrogen (+) tartrate (165 mg/l) in the tap water). Catecholamine fluorescence was evaluated using quantitative histofluorometry on brain sections treated according to Falck-Hillarp methodology. In order to evaluate catecholamine utilization in discrete hypothalamic catecholamine nerve terminal networks, the alphaMT- (alpha-methyl-(+/-)-p-tyrosine methyl ester) induced catecholamine disappearance was studied 2 h following the tyrosine hydroxylase inhibition. The body weight was reduced in both the male and female rats from 3 weeks of age until 9 weeks of age following pre- and postnatal treatment with nicotine. Following one week of withdrawal from pre- and postnatal treatment with nicotine, an increased catecholamine utilization was observed in the medial and lateral palisade zones of the median eminence mainly in the female rat. In the female rat, reduced prolactin serum levels were found both in the presence and absence of alphaMT treatment as well as reduced luteinizing hormone concentration in the presence of alphaMT treatment. At 6 months of age indications of a maintained, weak activation of the catecholamine nerve terminal systems in the medial palisade zones of the median eminence were observed in male rats pre- and postnatally treated with nicotine. Furthermore, increased noradrenaline levels were found in the paraventricular hypothalamic nucleus. An increase in serum luteinizing hormone levels was also found in these rats. In the 7-month old diestrous rat, maintained marked increases in catecholamine utilization in the medial and lateral palisade zones of the median eminence were found following treatment with nicotine during the pre- and postnatal period. A significant reduction of nigral dopamine stores was also demonstrated. The serum levels of thyroid stimulating hormone, prolactin and luteinizing hormone were unchanged in these rats both in the presence and absence of tyrosine hydroxylase inhibition. Finally, pre- and postnatal treatment with nicotine did not alter [(3)H]nicotine binding (quantitative receptor autoradiography) in cortical, striatal and thalamic areas of the adult diestrous rat. The results demonstrate that pre- and postnatal treatment with nicotine in the drinking water produces permanent activations of the catecholamine nerve terminal networks of the external layer of the median eminence mainly in the female rat. These changes appear to be associated with reduced serum prolactin levels in the 4-week old female rat. Sex-specific changes occur in discrete noradrenaline nerve terminal systems. The observed changes may have functional consequences for neuroendocrine regulation and for the regulation of food and water intake as well as sex-specific responses to stress in the male versus the female rat. Nicotine-induced disturbances in brain cell replication and differentiation may underlie the permanent alteration found in discrete catecholamine neuron systems after pre- and postnatal exposure to this drug.

Persistent effects of neonatal toluene exposure on regional brain catecholamine levels and turnover in the adult male rat

Effects of neonatal toluene exposure (80 ppm, day 1–7, 6 h/day) have been studied on regional brain catecholamine levels and utilization, and on serum levels of hypophyseal and adrenocortical hormones in the adult male rat. Catecholamine levels were measured by quantitative histofluorimetry in the forebrain and hypothalamus and by high pressure liquid chromatography with electrochemical detection in the substantia nigra. Catecholamine utilization was evaluated from the decrease in catecholamines seen after tyrosine hydroxylase inhibition using α-methy- p-tyrosine methyl ester hydrochloride (αMT, 250 mg/kg, i.p., 2 h). Serum levels of thyroid stimulating hormone, corticosterone, aldosterone, prolactin and luteinizing hormone were measured by radioimmunoassays. Neonatal toluene exposure produced a reduction of dopamine levels and utilization selectively in the olfactory tubercle and substantia nigra of the adult rat. Furthermore, neonatal toluene exposure produced a significant reduction in the noradrenaline levels and utilization in the substantia nigra and an increase of noradrenaline utilization selectively in the subependymal layer of the median eminence and of the magnocellular part of the paraventricular hypothalamic nucleus. The serum hormone levels were not significantly influenced by neonatal toluene exposure as evaluated in adulthood. However, the αMT induced increase in serum prolactin levels was reduced following neonatal exposure to toluene. Neonatal toluene treatment was also found to alter the responses of the catecholamine neurons to subacute toluene exposure in adulthood. In some of the dopamine nerve terminal systems of the forebrain and in the dopamine cell body containing area of the substantia nigra neonatal toluene exposure appears to have made the dopamine neurons insensitive to adult subacute toluene exposure. In the hypothalamic noradrenaline nerve terminal systems, there were even reversed responses to subacute toluene exposure. The present results indicate that neonatal toluene exposure in doses at the threshold limit value produces persistent changes in dopamine and noradreneline neurons of the forebrain, hypothalamus and substantia nigra in the presence of a relatively intact neuroendocrine system. In addition, neonatal toluene exposure appears to diminish or even counteract the responses to subacute toluene treatment in adulthood.

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.

Involvement of D1 dopamine receptors in the nicotine-induced noradrenaline release from hypothalamic and preoptic noradrenaline nerve terminal systems

Nicotine (4 x 2 mg/kg, i.p.) was given every 30 min for 2 h to male rats. Some rats were pretreated with the D1 dopamine (DA) receptor antagonist SCH 23390 (1 mg/kg, i.p.) or with the D2 DA receptor antagonist raclopride (1 mg/kg, i.p.), 5 min before nicotine treatment. Hypothalamic and preoptic catecholamine levels were measured by quantitative histofluorimetry in discrete DA and noradrenaline nerve terminal systems. Nicotine treatment produced a depletion of catecholamine stores in noradrenaline and DA nerve terminals of the hypothalamus, the preoptic area and the median eminence, an action which was counteracted by SCH 23390 but not by raclopride. The results indicate that hypothalamic D1 DA receptors may regulate the sensitivity of the nicotinic cholinoceptors and increase their ability to release hypothalamic noradrenaline. A possible role of D1 DA receptor antagonists to reduce the ability of nicotine treatment to produce rapid increases in LH, prolactin and corticosterone secretion and tonic arousal is implicated.

The effects of acute and chronic treatment with triiodothyronine and thyroxine on the hypothalamic and telencephalic catecholamine nerve terminal systems of the hypophysectomized male rat. Chronic treatment modulates catecholamine utilization in discrete catecholamine nerve terminal systems.

Using catecholamine (CA) fluorescence histochemistry in combination with quantitative microfluorimetry, it has been shown that chronic treatment with triiodothyronine (T3) and thyroxine (T4; 2 X 10 and 2 X 36 micrograms/kg i.p., respectively, twice daily for 10 days), but not acute treatment (1 and 3.6 mg/kg i.p., respectively, 2 h before killing), increases CA utilization in the medial and lateral palisade zones of the median eminence and reduces noradrenaline (NA) utilization in the parvocellular part and magnocellular part of the paraventricular hypothalamic nucleus of the hypophysectomized male rat. Following chronic T4 treatment it could also be shown that the CA levels in the medial and lateral palisade zones of the median eminence were increased, while the NA levels were reduced in the parvocellular part of the paraventricular hypothalamic nucleus. Chronic T3 treatment induced similar changes - increased CA levels in the medial palisade zone and reduced NA levels in the magnocellular part of the paraventricular hypothalamic nucleus. Within the telencephalon, chronic but not acute treatment with T3 or T4 selectively increased dopamine (DA) utilization within the diffuse type of DA nerve terminal systems of the nucleus accumbens. This action of chronic treatment of T3 or T4 was highly selective and no changes in DA levels could be demonstrated in any DA nerve terminals analyzed in the nucleus caudatus putamen; nucleus accumbens and tuberculum olfactorium. In all the experiments the TSH levels remained undetectable and the low basal serum prolactin levels were not modulated in any experimental group in spite of the treatment with a tyrosine hydroxylase inhibitor in the CA utilization experiments. Following 2-3 weeks after hypophysectomy, serum T3 and T4 were decreased by 30-50%. In the acute experiments with T3 or T4, serum T3 levels and T3 as well as T4 levels were markedly elevated after the respective treatments. In the chronic experiments, the T4 treatment resulted in significant increases in the serum levels of both T3 and T4. The present results indicate that discrete DA and NA nerve terminal systems within the median eminence (DA), nucleus accumbens (DA) and paraventricular hypothalamic nucleus (NA) can slowly respond to chronic treatment with T3 or T4. This effect is the result of a direct action of the thyroid hormones on the brain since TSH is absent in the hypophysectomized rat.(ABSTRACT TRUNCATED AT 400 WORDS)

Regression analysis of catecholamine utilization in discrete hypothalamic and forebrain regions of the male rat: effects of thyroidectomy

The effects of thyroidectomy (4 weeks) on dopamine (DA) and noradrenaline (NA) turnover rates were determined by means of regression analysis. The disappearance of catecholamine (CA) fluorescence (using quantitative histofluorimetry) after tyrosine hydroxylase inhibition (alpha-methyl-DL-p-tyrosine methyl ester) has been investigated in discrete hypothalamic and forebrain DA and NA nerve terminal systems of the male rat. A time-dependent monophasic CA fluorescence disappearance was observed in all CA nerve terminal systems of the sham-operated and thyroidectomized rats. In the thyroidectomized rat, DA turnover in the anterior nucleus accumbens and in the medial and lateral palisade zones of the median eminence (ME) was reduced while DA turnover in the posterior nucleus accumbens was increased as compared to control rats. Furthermore, NA turnover was increased in the paraventricular hypothalamic nucleus (PA) and reduced in the dorsomedial hypothalamic nucleus (DM) and in the 'border zone' (lateral hypothalamus). Radioimmunoassay of hormones in serum demonstrated marked increases in TSH levels and reduced concentrations of GH, prolactin, corticosterone, triiodothyronine and thyroxine. The reduced DA turnover in the external layer of the ME and the increased NA turnover in the PA may indicate an inhibitory dopaminergic mechanism in the ME and a facilitatory noradrenergic mechanism in the PA in the regulation of TSH secretion. These mechanisms seem to interact with thyroid hormones. The reduced NA turnover demonstrated in the DM and in the border zone may be related to the lowering of growth hormone levels and pulsatility caused by thyroidectomy. Finally, the DA nerve terminal systems in the anterior and posterior parts of the nucleus accumbens are differently regulated by changes in the brain-pituitary-thyroid axis.

Differential effects of mecamylamine on the nicotine induced changes in amine levels and turnover in hypothalamic dopamine and noradrenaline nerve terminal systems and in the secretion of adenohypophyseal hormones in the castrated female rat. Evidence for involvement of cholinergic nicotine-like receptors.

The effects of mecamylamine on the nicotine induced changes in hypothalamic catecholamine (CA) levels and turnover in female rats ovariectomized for one month have been evaluated using a quantitative microfluorimetric approach to measure CA levels in sections of brains treated according to the Falck-Hillarp procedure for the cellular demonstration of CA. In the same group of animals the serum prolactin, LH, FSH, TSH, GH and corticosterone levels were measured using radioimmunoassay procedures. The nicotine treatment induced a significant depletion of amine stores and an increase of amine turnover in dopamine (DA) and noradrenaline (NA) nerve terminals of the median eminence and of the peri- and paraventricular and dorsomedial NA systems of the hypothalamus using the tyrosine hydroxylase (TH) inhibition model. Mecamylamine (2 X 1 mg/kg) partly counteracted the nicotine induced reduction of amine stores in peri- (anterior part) and paraventricular NA nerve terminal systems as well as the nicotine induced increase of NA turnover in these systems, but not the action of nicotine on the CA systems of the median eminence. Nicotine (4 X 2 mg/kg) significantly and markedly reduced prolactin, LH, TSH, and GH secretion increased corticosterone secretin but did not influence FSH secretion. These effects were partly counteracted by mecamylamine (2 X 1 mg/kg) in the case of prolactin, LH and TSH secretion but not in the case of GH and corticosterone secretion. Taken together the results show that mecamylamine treatment (2 X 1 mg/kg) differentially counteract nicotine induced changes of amine levels and turnover in peri- (anterior part) and paraventricular NA nerve terminal systems indicating that the cholinergic nicotine-like receptors located in peri- (anterior part) and paraventricular areas may be more susceptible to the blocking activity of mecamylamine than those located in the median eminence area. Furthermore, the inhibitory effects of nicotine on prolactin, LH and TSH secretion are differentially counteracted by mecamylamine. In conclusion, other inhibitory systems than the tuberoinfundibular DA neurons in the MPZ and LPZ must also be involved in mediating the inhibitory effects of nicotine on prolactin, LH and TSH secretion and different types of cholinergic nicotine-like receptors may exist.

Central catecholamine neurons and exposure to dichloromethane. Selective changes in amine levels and turnover in tel- and diencephalic DA and NA nerve terminal systems and in the secretion of anterior pituitary hormones in the male rat

Subacute exposure of male rats to various concentrations (70–1000 ppm) of dichloromethane (DCM) produces a selective reduction of dopamine (DA) levels without a change of DA turnover in certain types of forebrain DA nerve terminal systems. In the low concentration (70 ppm) a selective reduction of DA turnover was observed in the medial palisade zone (MPZ) of the median eminence. This chlorinated organic solvent also produced a discrete dose-dependent increase of noradrenaline (NA) turnover within the

Rapid and discrete changes in hypothalamic catecholamine nerve terminal systems induced by audiogenic stress, and their modulation by nicotine — Relationship to neuroendocrine function

The effects of acute audiogenic stress, with or without simultaneous nicotine treatment (0.3 mg/kg i.v.), on catecholamine levels in discrete dopamine and noradrenaline nerve terminal systems of the hypothalamus, and on the secretion of adenohypophyseal hormones and of corticosterone, were studied using quantitative microfluorometric evaluations of catecholamine stores and radioimmunoassays for the determination of serum hormone levels. Audiogenic stress and nicotine induced very rapid and discrete decreases in noradrenaline levels in the subependymal layer (SEL), in the parvocellular part of nuc. paraventricularis hypothalamic (PA FP) and in the posterior periventricular hypothalamic systems, (PV II); the decreases were apparent 2 min following the onset of treatment. Increases of arterial blood pressure were observed after nicotine treatment but could not have been a major factor in producing the changes in catecholamine levels. These changes in NA levels may be related to the nicotine- and stress-induced increases of ACTH (SEL and PA FP) and prolactin secretion (PV II) found in the present experiments. Stress enhanced the rapid but variable increase in vasopressin secretion induced by nicotine, suggesting one possible mechanism by which stress combined with smoking can contribute to the development of increased arterial blood pressure and finally to sustained hypertension.

Involvement of cholinergic nicotine-like receptors as modulators of amine turnover in various types of hypothalamic dopamine and noradrenaline nerve terminal systems and of prolactin, LH, FSH and TSH secretion in the castrated male rat.

The effects of high repeated subcutaneous doses (4 X 2 mg/kg) of nicotine have been evaluated on dopamine (DA) and noradrenaline (NA) levels and turnover in the long-term castrated male rat using catecholamine (CA) fluorescence histochemistry in combination with quantitative microfluorometry. The CA turnover was evaluated by studying the decline of the CA stores following tyrosine hydroxylase inhibition using alpha-methyltyrosine methyl ester (H 44/68). In the same experiments trunk blood was collected for the determination of serum prolactin, LH, FSH and TSH levels using standard radioimmunoassay procedures. The nicotine treatment produced a significant depletion of CA stores and an increase of CA turnover in DA and NA nerve terminals of the median eminence and in peri- and paraventricular NA systems. These effects were significantly counteracted by pretreatment with mecamylamine. Nicotine significantly reduced serum prolactin and TSH levels, and after H 44/68 it also reduced LH and FSH serum levels. These actions were counteracted by mecamylamine pretreatment, except the effects on serum TSH levels after H 44/68, which were even enhanced by pretreatment with mecamylamine. Overall intraindividual correlations showed a significant correlation between reduced CA turnover in several hypothalamic areas and increased serum LH and FSH levels, increased NA turnover in the paraventricular hypothalamic nucleus and increased serum TSH levels, and reduced DA turnover in the median eminence and increased serum LH levels. It is suggested that in the castrated male rat nicotine can activate cholinergic nicotine-like receptors facilitating DA and NA turnover and release in various hypothalamic CA nerve terminal systems including those inhibiting the secretion of prolactin and LH (DA terminals in medial and lateral palisade zone, respectively) and facilitating secretion of TSH (NA terminals in the parvocellular part of the paraventricular hypothalamic nucleus).

Nicotine-induced increases of noradrenaline turnover in discrete noradrenaline nerve terminal systems of the hypothalamus and the median eminence of the rat and their relationship to changes in the secretion of adenohypophyseal hormones.

The effects of acute single doses (0.3 and 1 mg/kg) of nicotine on various hypothalamic catecholamine nerve terminal systems and on the secretion of adenohypophyseal hormones in the rat were studied. Nicotine, in a dose of 1.0 mg/kg, increased noradrenaline turnover in the median eminence and in the peri- and paraventricular hypothalamic regions. The dopamine and noradrenaline nerve terminal systems in the median eminence and the dorsomedial hypothalamic nucleus respectively were unaffected. Serum GH levels were decreased and serum prolactin levels increased after a dose of 1 mg/kg. In the presence of tyrosine hydroxylase inhibition, nicotine in a dose of 1 mg/kg, instead increased GH and also LH secretion. It is suggested that the preferential increases of noradrenaline turnover in various hypothalamic noradrenaline nerve terminal systems by nicotine may be partly responsible for the nicotine induced increases of serum prolactin. GH and LH levels observed.