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).     

Mecamylamine pretreatment counteracts cigarette smoke induced changes in hypothalamic catecholamine neuron systems and in anterior pituitary function

We have studied the effects of acute, intermittent exposure to tobacco smoke on discrete hypothalamic CA nerve terminal networks and on neuroendocrine function by means of quantitative histofluorimetrical determinations of catecholamine (CA) fluorescence in sections of rat brain and by radioimmunoassay procedures for hormones. Acute intermittent exposure to cigarette smoke induced a lowering of NA levels and increased NA turnover in discrete hypothalamic nerve terminal regions. This exposure also induced increases in DA turnover in the median eminence. The cigarette smoke lowered TSH, prolactin, LH and FSH serum levels, but induced an increase in serum corticosterone concentrations. To determine if the above mentioned changes in neuroendocrine function were nicotine mediated, a cholinergic nicotine-like blocking agent, mecamylamine, was administered prior to exposure to cigarette smoke. Pretreatment with mecamylamine (1.0 mg kg-1) counteracted the cigarette smoke induced changes in CA levels and turnover in all hypothalamic CA nerve terminal regions as well as the changes in serum levels of the pituitary hormones and corticosterone. It is suggested that acute intermittent exposure to cigarette smoke, via its nicotine component, lowers TSH, prolactin, LH and FSH secretion at least in part through activation of the tubero-infundibular DA neurons. Furthermore, the nicotine component of the cigarette smoke is suggested to induce the increase in corticosterone serum levels via increasing NA turnover in the paraventricular hypothalamic nucleus.     

Effects of acute intermittent exposure to cigarette smoke on catecholamine levels and turnover in various types of hypothalamic DA and NA nerve terminal systems as well as on the secretion of adenohypophyseal hormones and corticosterone

Male rats were exposed to cigarette smoke (Walton Horizontal Smoking Machine) from one to four cigarettes (Kentucky reference IR-1 type). Catecholamines in the diencephalon were measured by quantitative histofluorimetry in discrete dopamine (DA) and noradrenaline (NA) nerve terminal systems. Blood TSH, prolactin, LH, FSH, ACTH, vasopressin and corticosterone levels were determined by radioimmunoassay procedures. Exposure to unfiltered, but not to filtered (Cambridge glass fibre filters) cigarette smoke resulted in dose-dependent reductions of NA levels in the various hypothalamic NA nerve terminal systems. Evidence was obtained that exposure to unfiltered but not to filtered cigarette smoke resulted in dose-dependent increases of amine turnover (alpha MT-induced CA disappearance experiments) in the various DA and NA nerve terminal systems in the hypothalamus. The lowering of TSH, LH and prolactin secretion induced by unfiltered smoke were probably induced by nicotine and were independent of tyrosine hydroxylase inhibition. Furthermore, unfiltered cigarette smoke produced a dose-related increase in corticosterone secretion. The inhibitory effects of TSH, LH and prolactin secretion were probably in part related to the ability of unfiltered smoke via its nicotine component to activate the lateral and medial tubero-infundibular DA neurons. The increases in corticosterone secretion may at least in part be related to a smoke induced increase in the facilitatory influence of paraventricular NA nerve terminals on CRF activity.     

Immobilization stress-induced changes in discrete hypothalamic catecholamine levels and turnover, their modulation by nicotine and relationship to neuroendocrine function

Immobilization stress (1 h) induced discrete reductions in noradrenaline (NA) levels in the posterior periventricular hypothalamic region and in the paraventricular hypothalamic nucleus, and a decrease in dopamine (DA) turnover in the medial palisade zone (MPZ) of the median eminence, but failed to induce regional increases of hypothalamic NA turnover. Stress also stimulated the secretion of ACTH, corticosterone and prolactin, while vasopressin, LH and FSH serum levels were unaffected. The stress induced reduction of DA turnover in MPZ may mediate the stress induced increase of prolactin secretion. Nicotine (0.3 mg/kg, s.c., 1 h) did not by itself significantly influence catecholamine (CA) turnover in the various CA nerve terminal systems analyzed in the hypothalamus, but reduced NA levels in the subependymal layer (SEL) of the median eminence. Nicotine administration did not affect the serum levels of any of the hormones evaluated. Nicotine counteracted to a minor degree the immobilization stress-induced reduction in NA levels, and also the stress-induced secretion of ACTH, but not of prolactin suggesting the involvement of noradrenergic mechanisms possibly in the paraventricular nucleus in the nicotine modulation of stress induced increases of ACTH secretion. The nicotine-induced reduction of NA levels in SEL was blocked by stress as well as the tendency for nicotine induced increases of dopamine (DA) turnover in the medial and lateral palisade zones of the median eminence indicating opposing influences of immobilization stress and nicotine on at least some hypothalamic CA systems.     

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.     

Determinations of catecholamine half-lives and turnover rates in discrete catecholamine nerve terminal systems of the hypothalamus, the preoptic region and the forebrain by quantitative histofluorimetry

To determine whether amine pool sizes, half-lives and turnover rates could be measured in discrete hypothalamic, preoptic and forebrain catecholamine (CA) nerve terminal networks by quantitative histofluorimetry, the CA fluorescence disappearance was studied at different time intervals after tyrosine hydroxylase inhibition. For comparison, the depletion of DA and NA following tyrosine hydroxylase inhibition in discrete brain regions was determined by high pressure liquid chromatography (HPLC). Following tyrosine hydroxylase inhibition using alpha-methyl-DL-p-tyrosine methyl ester, an apparently monophasic decline of the CA stores was demonstrated in all brain regions analysed both histochemically and by HPLC. A multiphasic DA disappearance was measured by HPLC in the peri- and paraventricular hypothalamic area. The DA nerve terminal networks generally had shorter half-lives than the NA nerve terminal networks. The shortest half-life (99 min) of the regions demonstrating a monophasic decline of CA stores was found in the CA nerve terminal system in the medial palisade zone of the median eminence. By the use of CA standards in the histochemically prepared sections, it was possible to convert the measured CA fluorescence into absolute amounts of catecholamines expressed in nmol X g-1 of tissue wet weight. It was shown that the CA stores and the turnover rates measured by quantitative histofluorimetry were 20-30 times greater than those measured using HPLC. The difference has been related to amine dilution with amine-poor areas in the specimens analysed by HPLC. By studying the accumulation of catecholamines after monoamine oxidase inhibition, it could be demonstrated that no concentration-dependent quenching of CA fluorescence occurred.     

Unique responses to mitochondrial complex I inhibition in tuberoinfundibular dopamine neurons may impart resistance to toxic insult

Tuberoinfundibular dopamine (TIDA) neurons are spared in Parkinson's disease (PD), a disorder that causes degeneration of midbrain nigrostriatal dopamine (NSDA) and mesolimbic dopamine (MLDA) neurons. This pattern of susceptibility has been demonstrated in acute complex I inhibitor-induced models of PD, and extrinsic factors such as toxin distribution, bioactivation, entry into the cell and sequestration into vesicles are postulated to underlie the resistance of TIDA neurons. In the present experiments, direct exposure to rotenone or 1-methyl-4-phenylpyridinium (MPP+) had no effect on mediobasal hypothalamic TIDA neurons, but significantly increased the percentage of apoptag immunoreactive neurons in midbrain primary NSDA and MLDA cultures. In vivo 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) exposure caused an initial decrease (by 4 h) in dopamine (DA) in brain regions containing axon terminals of TIDA (median eminence [ME]), NSDA (striatum [ST]) and MLDA (nucleus accumbens [NA]) neurons. By 16 h after MPTP treatment, DA concentrations in ME returned to control levels, while ST and NA DA levels remained low up to 32 h after treatment with MPTP. When mice and rats were chronically treated with MPTP and rotenone, respectively, the same pattern of susceptibility emerged. TIDA neurons were unaffected while NSDA neurons suffered loss of cell bodies and axon terminal DA. These experiments demonstrate that the resistance of hypothalamic TIDA neurons is not likely to be due to extrinsic factors, and that further examination of the intrinsic properties of these neurons may elucidate mechanisms that can be translated into neuroprotective strategies in PD.     

Effects of acute haloperidol treatment on regional catecholamine levels and utilization in rats exposed to toluene

The aim of the present investigation was to evaluate whether the responses of central catecholamine (CA) neurons to CA receptor blockade by haloperidol are altered upon toluene exposure. Male rats were exposed to air or toluene (80 ppm) for 5 and 4 days, 6 h day^-1. CA levels and utilization were determined in discrete regions of the forebrain and hypothalamus as well as in the substantia nigra (SN) and anteromedial frontal cortex (AMFC). Serum levels of corticosterone, thyroid stimulating hormone, luteinizing hormone and prolactin were determined by radioimmunoassay procedures. Toluene exposure led to increased dopamine (DA) utilization in the AMFC and increased CA utilization in the paraventricular hypothalamic nuclei. In air-exposed rats haloperidol (1 mg kg^-1, i.p., 2 h before killing) increased DA utilization in the marginal part of the nucleus caudatus putamen (CAUD). In toluene-exposed rats, haloperidol induced significant depletions of DA stores in the SN and in the medial and central parts of the CAUD. In the posterior nucleus accumbens (ACC) DA utilization was significantly increased. Combined haloperidol and toluene treatment selectively decreased DA levels in the ACC and SN, and significantly increased DA utilization in the CAUD, as compared with the air-exposed control group. Furthermore, after combined treatment, there was a specific increase in noradrenaline (NA) utilization in the SN and in CA utilization in the medial palisade zone of the median eminence. Serum prolactin levels were substantially raised in both the air and toluene groups after the haloperidol treatment. In conclusion, acute haloperidol treatment preferentially reduces DA levels and increases DA and NA utilization in the SN and in discrete tel- and diencephalic areas in rats exposed to toluene.     

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.     

Thyrotropin releasing hormone (TRH): its changes in discrete hypothalamic areas after treatment with triiodothyronine, thyroidectomy and acute cold exposure

In order to elucidate the specific thyrotropic area in the hypothalamus, thyrotropin releasing hormone (TRH) content and concentration were measured in discrete hypothalamic nuclei and areas after triiodothyronine (T3) administration (T3 10 micrograms/rat/day for 6 days), thyroidectomy (TX) and acute cold exposure in male rats. In th TX and T3 groups, serum TSH levels were significantly increased in TX group and markedly decreased in T3 and TX with T3 groups as compared to the sham operated control group (Sham). TX produced a slight but nonsignificant decrease in TRH content in most of the hypothalamic nuclei examined as compared with the Sham group. However, a significant increase in TRH contents was seen in the anterior hypothalamic nucleus (AHN), median eminence (ME) and posterior pituitary (PP) in TX with T3 group as compared to the rats with only TX. In the acute cold stress experiments, serum TSH levels were elevated from 15 to 30 min of 4 degrees C exposure. Together with these peripheral changes, TRH content and concentration in the suprachiasmatic nucleus (SC) were increased significantly at 15 min and had returned to the normal level by 30 min after 4 degrees C cold exposure. However, in the paraventricular nucleus (PV) and dorsal premammillary nucleus (PMD), marked decrease in TRH concentrations were observed with this stress. Therefore, 1) decreased TSH release in TX rats treated with T3 was induced by the block of TRH release from the AHN and ME as compared with the TX group, and 2) elevated serum TSH levels in 4 degrees C cold stress might be induced by the release of TRH from the PMD and PV. These experiments demonstrate that the specific hypothalamic area for TSH release was located in some of the anterior and posterior hypothalamic nuclei and in the ME.     

Temporal changes in medial basal hypothalamic catecholamines in male Syrian hamsters exposed to short photoperiod

Summary The gonadal and accessory organ atrophy following transfer of male hamsters from long (LP) to short photoperiod (SP) is preceded by reduced prolactin secretion and involves reductions in hypothalamic LHRH release and catecholamine turnover. These experiments examined the temporal aspects of changes in medial basal hypothalamic/ median eminence (MBH/ME) catecholamine turnover rates in male hamsters undergoing SP-induced gonadal atrophy. Hamsters were sacrificed at three, six, nine and twelve weeks of SP exposure. MBH/ME catecholamines and indoleamines were determined by high performance liquid chromatography coupled with electrochemical detection. Reductions in serum prolactin (PRL) levels and increased MBH/ME dopamine (DA) turnover rates were observed at three and six weeks of SP exposure. Both steady state concentrations and turnover rates of norepinephrine (NE) and DA were depressed after nine and twelve weeks of SP exposure, at which time testicular and accessory organ atrophy had occurred. Serotonin (5-HT) and 5-hydroxy-3-indoleacetic acid (5-HIAA) concentrations were insignificantly changed during the period of SP treatment but the 5-HIAA/5-HT ratio was significantly increased after six weeks of SP exposure. It was concluded that increased MBH/ME DA turnover represents an initial, SP-induced neuroendocrine event. This increase in DA turnover probably contributes to the reduced PRL secretion which precedes, and may play a role in the ensuing gonadal and accessory organ atrophy.     

Effects of a postnatal exposure to cigarette smoke on hypothalamic catecholamine nerve terminal systems and on neuroendocrine function in the postnatal and adult male rat. Evidence for long-term modulation of anterior pituitary function.

The purpose of this paper was to study the possible long-term effects of postnatal exposure to cigarette smoke. Male Sprague-Dawley rats were exposed to the smoke from 2 cigarettes (Kentucky reference IR-1 type) every morning from day 1 after birth for a period of 5, 10 or 20 days. The rats were decapitated 24 hours (5, 10 and 20 days of exposure), 1 week (20 days of exposure) or 7 months (20 days of exposure) after the last exposure. Using the Falck-Hillarp methodology in combination with quantitative histofluorimetry catecholamine levels and changes in catecholamine utilization (alpha MT-induced CA fluorescence disappearance) in discrete hypothalamic catecholamine nerve terminal systems were analysed. Serum prolactin, LH, TSH and corticosterone levels were determined by means of radioimmunoassay procedures. In the postnatal period serum LH levels were significantly increased 24 hours after a 10 and 20 day exposure to cigarette smoke. In adult life after a 20-day postnatal exposure to cigarette smoke a highly significant increase was observed in serum prolactin levels, which were unaltered by this exposure when measured in the postnatal period. Twenty-four hours following a 20-day postnatal exposure, catecholamine utilization was increased in the medial palisade zone of the median eminence and substantially reduced in the parvocellular and magnocellular parts of the paraventricular hypothalamic nucleus. One week and 7 months following a 20-day postnatal exposure to cigarette smoke no alterations were observed in catecholamine levels or utilization in various hypothalamic areas including the median eminence. All the above changes were observed in the presence of an unaltered development of body weight. The results indicate that marked but temporary increases in LH secretion occur 24 hours after a postnatal exposure to cigarette smoke, while increase in prolactin secretion only develop in adult life, when the maturational processes of the brain and/or the anterior pituitary gland are completed. Changes in catecholamine levels and utilization are found in discrete hypothalamic nerve terminal networks but do not play a major role in mediating the above changes in anterior pituitary function and are probably the result of a withdrawal phenomenon.     

Effects of a postnatal exposure to cigarette smoke on hypothalamic catecholamine nerve terminal systems and on neuroendocrine function in the postnatal and adult male rat. Evidence for long-term modulation of anterior pituitary function

Jansson , A., Anderson , K., Bjelke , B., Fuxe , K. & Eneroth , P. 1991. Effects of a postnatal exposure to cigarette smoke on hypothalamic catecholamine nerve terminal systems and on neuroendocrine function in the postnatal and adult male rat. Evidence for long-term modulation of anterior pituitary function. Acta Physiol Scand. 144 , 453–462. Received 10 August 1 991 , accepted 11 August 1991. ISSN 0001–6772. Department of Histology and Neurobiology, Karolinska Instituter, Stockholm, Sweden, Department of Internal Medicine and Unit for Applied Biochemistry, Huddinge Hospital, Huddinge, Sweden. The purpose of this paper was to study the possible long-term effects of postnatal exposure to cigarette smoke. Male Sprague-Dawley rats were exposed to the smoke from 2 cigarettes (Kentucky reference IR-I type) every morning from day 1 after birth for a period of 5 , 10 or 20 days. The rats were decapitated 24 hours ( 5 , 10 and 20 days of exposure), 1 week (20 days of exposure) or 7 months (20 days of exposure) after the last exposure. Using the Falck-Hillarp methodology in combination with quantitative histofluorimetry catecholamine levels and changes in catecholamine utilization (aMT-induced CA fluorescence disappearance) in discrete hypothalamic catecholamine nerve terminal systems were analysed. Serum prolactin, LH, TSH and corticosterone levels were determined by means of radioimmunoassay procedures. In the postnatal period serum LH levels were significantly increased 24 hours after a 10 and 20 day exposure to cigarette smoke. In adult life after a 20–day postnatal exposure to cigarette smoke a highly significant increase was observed in serum prolactin levels, which were unaltered by this exposure when measured in the postnatal period. Twenty-four hours following a 20–day postnatal exposure, catecholamine utilization was increased in the medial palisade zone of the median eminence and substantially reduced in the parvocellular and magnocellular parts of the paraventricular hypothalamic nucleus. One week and 7 months following a 20–day postnatal exposure to cigarette smoke no alterations were observed in catecholamine levels or utilization in various hypothalamic areas including the median eminence. All the above changes were observed in the presence of an unaltered development of body weight. The results indicate that marked but temporary increases in LH secretion occur 24 hours after a postnatal exposure to cigarette smoke, while increase in prolactin secretion only develop in adult life, when the maturational processes of the brain and/or the anterior pituitary gland are completed. Changes in catecholamine levels and utilization are found in discrete hypothalamic nerve terminal networks but do not play a major role in mediating the above changes in anterior pituitary function and are probably the result of a withdrawal phenomenon.     

The effects of D1 or D2 dopamine receptor antagonism in the medial preoptic area, ventral pallidum, or nucleus accumbens on the maternal retrieval response and other aspects of maternal behavior in rats

The medial preoptic area (MPOA), ventral pallidum (VP), and nucleus accumbens (NA) receive dopaminergic afferents and are involved in maternal behavior. Experiments investigated whether dopamine (DA) receptor antagonism in NA disrupts maternal behavior, determined the type of DA receptor involved, and investigated the involvement of drug spread to VP or MPOA. Injection of SCH 23390 (D1 DA receptor antagonist) into NA of postpartum rats disrupted retrieving at dosage levels that were ineffective when injected into MPOA or VP. Motor impairment was not the cause of the deficit. Injection of eticlopride (D2 DA receptor antagonist) into NA or VP was without effect. Results emphasize the importance of DA action on D1 receptors in NA for retrieval behavior.     

The influence of salsolinol on dopaminergic system activity within the mediobasal hypothalamus of anestrous sheep: a model for studies on the salsolinol-dopamine relationship

Salsolinol with its derivatives has been considered as a potential neurotoxin for the dopaminergic system in the human and rat brain. Investigating a sheep model for studies on the action of salsolinol within the central nervous system we examined whether this compound is able to affect the hypothalamic neuroendocrine dopaminergic (NEDA) system during its high seasonal activity, when sheep entered to anestrus under the long day conditions. Therefore, salsolinol was infused into the third ventricle of the brain in combination with the in vivo push-pull perfusion of the mediobasal hypothalamus/median eminence (MBH/ME). The effects of this drug on either perfusate noradrenaline (NA) or plasma prolactin concentration were also studied. The infusion of salsolinol resulted in rapid and permanent diminution in dopamine (DA) release into the extracellular spaces of the MBH/ME up to an undetectable level and in the 57% decrease in DA metabolite 3,4-dihydroxyphenylacetic acid concentration, compared to the control. This effect of salsolinol was accompanied by the significant enhancement of the pituitary prolactin release into circulation. The concentration of other DA metabolite, homovanillic acid, as well as NA in the MBH/ME was not affected. Thus, our results in the anestrous sheep underline the role played by salsolinol as a neuromodulator for the hypothalamic NEDA system and as a signal transmitter for the pituitary prolactin release. We suggest that the hypothalamic NEDA system of anestrous sheep during its high secretory activity may be set as a model for studies on the salsolinol-dopamine relationship.     

Estradiol and song affect female zebra finch behavior independent of dopamine in the striatum

Female songbirds display preferences for certain song characteristics, but the neural and hormonal mechanisms mediating these preferences are not fully clear. The present study sought to further explore the role of estradiol, as well as assess potential roles of dopaminergic systems, on behavioral responses to song. Adult female zebra finches were treated with estradiol and exposed to tutored or untutored song or silence. Behavior was quantified and neurochemistry of the nucleus accumbens and striatum was examined with high performance liquid chromatography. As a control, the responses of these two systems to treatment with raclopride, a specific D2 receptor antagonist, were also evaluated. This manipulation did not affect dopamine (DA), but did increase DOPAC and the DOPAC/DA ratio. Estradiol reduced the display of two behaviors, distance calls and visual scanning, but had no effect on dopaminergic responses. Auditory stimulus exposure affected other vocalizations, but song presentation did not modulate the levels of DA or its metabolite, DOPAC in the nucleus accumbens or striatum. Collectively, the results suggest that both estradiol and auditory stimuli can modify the behavioral responses of adult zebra finches, but they may not change DA concentration or turnover in striatal dopamine neurons.     

Comparative study of dopamine- and noradrenaline-immunoreactive terminals in the paraventricular and supraoptic nuclei of the rat

The distribution of dopaminergic and noradrenergic terminal fields of the paraventricular (PVN) and supraoptic (SON) nuclei of the rat was investigated at the optic and electron microscopical level using antibodies directed against dopamine (DA) and noradrenaline (NA). The DA innervation was uniform among these nuclei, although more important in the PVN than in the SON. NA fibers were preferentially distributed in the parvocellular parts of the PVN and in areas of the magnocellular nuclei where vasopressinergic neurons were mainly located. Both DA and NA terminals synaptically contacted magnocellular neurons on their cell body or dendrites. This study thus provides morphological evidence for a double and independent catecholaminergic control, by DA and NA, on neuroendocrine mechanisms at the hypothalamic level.     

Effect of sex and age on brain monoamines and spatial learning in rats

The concentrations of noradrenaline (NA), dopamine (DA), serotonin (5-HT), and their metabolites were measured in the prefrontal cortex, caudate-putamen, and hippocampus in young (3 months) and aged (27–31 months) Wistar rats of both sexes. Age-related changes were found in prefrontal NA and HVA/DA ratio, striatal DA and DOPAC/DA ratio, and striatal and hippocampal 5-HT and 5-HIAA/5-HT ratio. Age and sex dependent changes were found in striatal DA and DOPAC/DA ratio, and hippocampal MHPG-SO₄/NA ratio. The aged rats were tested in spatial discrimination and reversal tasks in a T maze. The effects of α₂-agonist medetomidine (3 μg/kg) on the task performance were assessed in relation to individual variation in monoamine metabolism. Medetomidine impaired spatial discrimination learning of the aged rats by interacting with the hippocampal 5-HT turnover. Medetomidine improved reversal learning through an interaction with the striatal DA turnover and reduced the number of perseverative errors after reversal, mainly due to its interaction with the prefrontal NA turnover. It is concluded that the memory enhancing effect of drugs acting through the brain monoamine systems is highly dependent on the stage of degeneration of these systems that show considerable individual variation in aged animals.     

The neurotoxic actions of 1-methyl-4-phenylpyridine (MPP+) are not prevented by deprenyl treatment

1-Methyl-4-phenylpyridine (MPP+) injected into the cerebral ventricles (ICV) of mouse caused depletions of striatal dopamine (DA)(-42%), 3,4-dihydroxyphenylacetic acid (DOPAC) (-34%) and homovanillic acid (HVA) (-16%) content without significant reductions in levels of noradrenaline (NA), serotonin (5-HT) or 5-hydroxyindoleacetic acid (5-HIAA). When deprenyl was administered before MPP+, striatal DA and its metabolites were further depleted, and striatal NA and 5-HT levels also were reduced. Further, whilst ICV MPP+ alone failed to influence the biochemistry of the limbic areas (nucleus accumbens plus tuberculum olfactorium), in the presence of deprenyl MPP+ caused 20-40% reductions in levels of limbic NA, DA, DOPAC, HVA, 5-HT and 5-HIAA. Therefore, deprenyl treatment does not prevent the neurotoxic actions of MPP+; indeed, a more extensive neurotoxicity for MPP+ is revealed in the presence of this monoamine oxidase inhibitor.