Role of some biogenic amines in the pathomechanism of glomerulonephritis. II. Adrenaline, noradrenaline and serotonin in acute serum sickness in rabbits

In acute serum sickness induced with one intravenous dose of bovine serum albumin (BSA) in 40 rabbits the patterns of excretion of adrenaline (A), noradrenaline (NA), serotonin (5HT) and 5-hydroxyindole-acetic acid (5HIAA) were studied in 24-hour urine, and the 5HT level was determined at intervals of three days. The urinary levels of biogenic amines were determined daily. Some rabbits immunized with BSA received also additionally 5HT, reserpine or parachlorphenylalanine (PCPA). Administration of BSA to rabbits caused a significant increase in the excretion of A and NA and a less evident increase in 5HT level in the blood. The greatest correlation with the course of the immune reaction was shown by the increase in NA excretion observed on the 2nd and 3rd days after BSA administration, and then between the 5th and the 12th days of the experiment. Daily subcutaneous injections of 5HT during 15 days caused a significant rise of its level in the blood and urine, and an increase of 5HIAA excretion. After reserpine or PCPA administration a significant decrease of the levels of all these amines was observed. Taking into account the results of histological examination of the kidneys, that is intensification of the inflammatory changes after 5HT administration and evident inhibition of the inflammatory process after administration of reserpine and PCPA it must be accepted that the studied amines have an important role in the pathomechanism of glomerulonephritis in acute serum sickness.     

Experimenteller Beitrag zur Kenntnis der biogenen Amine im Glomus caroticum des Kaninchens

Zusammenfassung Der Einfluß von p-Chlorphenylalanin-methylester-hydrochlorid (PCPA) und Reserpin auf die biogenen Amine des Glomus caroticum von Kaninchen wurde ultrastrukturell und fluoreszenzmikroskopisch untersucht. Die elektronenmikroskopische Analyse ergab keine eindeutigen Kriterien für arzneimittelinduzierte Veränderungen. Fluoreszenzmikroskopisch ließ sich nach Applikation von Reserpin eine ausgeprägte Senkung des Catecholamin- und Indolamin-Gehaltes und nach PCPA eine Abnahme des Serotonins erkennen.

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Electron microscopic and fluorescence microscopic studies of biogenic amines in the rabbit glomus caroticum after treatment with reserpine and PCPA

Summary The effects of p-chlorophenylalanine-methylester-hydrochloride (PCPA) and reserpine on biogenic amines of the rabbit carotid body were investigated ultrastructurally and by fluorescence microscopy. The electron microscopic analysis did not indicate significantly that structural changes result from treatment with reserpine or PCPA. Fluorescence microscopy indicated that PCPA lowered serotonin, and reserpine lowered both catecholamines and indolamines.

Mit Unterstützung durch die Deutsche Forschungsgemeinschaft.     

An electron microscopic study on the effects of reserpine on the subclavian glomera of the rabbit.

Young male and female New Zealand white rabbits were given a daily subcutaneous injection of reserpine (Serpasil, Ciba; 3 mg/kg) for two days and were sacrificed 24 hours after the last injection. The subclavian glomera (aortic bodies) were processed for electron microscopy to determine the effects of this biogenic amine depleting agent on the electron-opaque cytoplasmic granules of the parenchymal type I cells. Observations of glutaraldehyde-osmium tetroxide fixed glomera from reserpinized animals showed a slight decrease in granule density of the type I cells. Glomera fixed in glutaraldehyde and incubated in potassium dichromate (pH 4.1) demonstrated a reduction in granule opacity following reserpine treatment. Control glomera incubated in potassium dichromate displayed electron-opaque granules. These results indicate that reserpine does deplete the amines without granule disappearance or changes in granule population. The positive reaction of the control tissue granules to potassium dichromate incubation suggests that the predominant biogenic amines in the electron-opaque granules are unsubstituted monoamines. Persistence of the opaque granules following reserpinization and glutaraldehyde-osmium tetroxide double fixation, may be due to amine-binding protein within the granules. The mode of granule depletion could not be ascertained with certainty.     

Synaptic loss following removal of serotoninergic fibers in newly hatched and adult chickens

Neurotransmitters such as serotonin (5HT) may have nontransmitter, trophic-like functions in the developing and adult nervous system. In order to examine this possibility in the avian spinal cord, we have quantified synapse numbers on spinal neurons following treatment with drugs that result in the destruction of 5HT positive axons. Either p-chlorophenylalanine or reserpine was injected into newly hatched or adult chickens. Following treatment for 7 days the density of nonserotoninergic synapses was considerably decreased in the targets of 5HT fibers. By contrast, neither change was observed in the dendritic structures of spinal motoneurons or in the distribution of substance P and enkephalin positive fibers. These data suggest that 5HT may play an important role in the normal increase and maintenance of synapses in developing and adult animals. A lesion of 5HT neurons may not only alter neurochemistry but also alter the general synaptic structures of the brain. While 5HT containing fibers were depleted in a dose-dependent fashion we cannot rule out the possibility that other neurotransmitter systems were depleted at higher dose of PCPA and reserpine. © 1993 John Wiley & Sons, Inc.     

Mikrospektrofluorometrische Untersuchungen der biogenen Amine im Glomus caroticum des Kaninchens nach Reserpin- und PCPA-Applikation

Zusammenfassung Die Glomera carotica von 12 Kaninchen wurden nach viertägiger Applikation von Reserpin (2 mg/kg KG; i.p.) (I), Parachlorphenylalanin-methylester-hydrochlorid (PCPA; 100 mg/kg KG; i.p.) (II) und physiologischer NaCl-Lösung (III) mit der Falckschen Fluoreszenzmethode aufgearbeitet und cytospektrofluorometrisch (Mikrospektrograph Leitz) ausgewertet.An Hand der Fluoreszenzspektren der spezifischen Glomuszellen (Typ I) ließ sich eine Depletion der Catecholamine und des Serotonins verfolgen: hiernach senkt PCPA vor allem das Serotonin, Reserpin hingegen die Catechol- und Indolamine in etwa gleichem Umfang.Durch Zerlegung einiger Gesamtspektren in die Anteile für Catecholamine und das Serotonin mit Hilfe eines Iterationsverfahrens der nichtlinearen Regression konnte gezeigt werden, daß nur eine geringfügige Beeinflussung der Catecholamin-Peakhöhe durch das Serotonin vorliegt. Über die Messung der Peakhöhe im Catecholaminbereich der Gesamtspektren konnte daher die Reduktion der Catecholamine auf 64±22% durch PCPA und auf 13±4% durch Reserpin statistisch gesichert werden.Die Befunde werden im Zusammenhang mit den möglichen Wirkungsmechanismen der applizierten Substanzen diskutiert. Eine ausführliche tabellarische Zusammenstellung der bisherigen Angaben über Gehalt und Zusammensetzung der biogenen Amine des Glomus caroticum ergänzt diese Diskussion.

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Microspectrofluorometric investigation of biogenic amines in the rabbit glomus caroticum after reserpine and PCPA treatment

Summary After the administration for 4 days of (I) reserpine (2 mg/kg body weight daily, i.p.), (II) p-chlorophenylalanine-methylester-hydrochloride (PCPA; 100 mg/kg body weight daily; i.p.) and III physiological NaCl solution, the carotid bodies of 12 rabbits were examined using Falck's fluorescence technique and evaluated cytospectrofluorometrically. Fluorescence spectra of the type I specific glomus cells revealed that a depletion of catecholamines and serotonin took place: PCPA lowered mainly serotonin, whereas reserpine depleted catechol- and indolamines about equally.It was shown by splitting of a few combined spectra with an iteration procedure of nonlinear regression, that serotonin affected slightly the height of the catecholamine peak. Thus, measuring the peak height in the catecholamine region of the total spectrum, the reduction of catecholamines to 64±22% by PCPA and to 13±4% by reserpine was statistically significant.These data are discussed in relation to possible mechanisms of action of the test substances and related to the content and nature of the biogenic amines in the carotid body.

Für technische Hilfe danken wir Fräulein B. Remki und Frau K. Wilp.     

Biogenic amines modulate pulse rate in the dorsal blood vessel of Lumbriculus variegatus

The biogenic amines are widespread regulators of physiological processes, and play an important role in regulating heart rate in diverse organisms. Here, we present the first pharmacological evidence for a role of the biogenic amines in the regulation of dorsal blood vessel pulse rate in an aquatic oligochaete, Lumbriculus variegatus (Müller, 1774). Bath application of octopamine to intact worms resulted in an acceleration of pulse rate, but not when co-applied with the adenylyl cyclase inhibitor MDL-12,330a. The phosphodiesterase inhibitor theophylline mimicked the effects of OA, but the polar adenosine receptor antagonist 8(p-sulphophenyl)theophylline was significantly less potent than theophylline. Pharmacologically blocking synaptic reuptake of the biogenic amines using the selective 5-HT reuptake blocker fluoxetine or various tricyclic antidepressants also accelerated heart rate. Depletion of the biogenic amines by treatment with the monoamine vesicular transporter blocker reserpine dramatically depressed pulse rate. Pulse rate was partially restored in amine-depleted worms after treatment with octopamine or dopamine, but fully restored following treatment with serotonin. This effect of 5-HT was weakly mimicked by 5-methoxytryptamine, but not by α-methylserotonin; it was completely blocked by clozapine and partially blocked by cyproheptadine. Because they are known to orchestrate a variety of adaptive behaviors in invertebrates, the biogenic amines may coordinate blood flow with behavioral state in L. variegatus.     

Significance of the reciprocal relationship of monoaminergic systems of the brain in the pharmacological compensation of 6-hydroxydopamine-induced behavior disorders in animals

The paper studied the methods of compensation of the abnormal emotional behaviour by means of pharmacological substances, which change the content of biogenic amines. The experiments made in the Wistar rats (n-54) whose frustration reaction was diminished by neonatal treatment of 6-OHDA. It was established that recovery of the disturbances in the frustration reaction in the animals with chronic brain system activity deprivation can be achieved not only by the activation of NA system (L-DOPA, DOPS) but also by deactivation of the 5-HT brain system activity (PCPA). These findings confirm suggestion about existence of reciprocal relationship between NA and 5-HT brain systems.     

Effect of several biogenic amines on in vitro progesterone secretion by the bovine corpus luteum

1. The effect of several biogenic amines on secretion of progesterone (P4) was examined using bovine corpora lutea (n = 6), removed on day 13 of the oestrus cycle, enzymatically dispersed and cultured in vitro. 2. Luteal cell cultures were co-incubated with 0, 10, 50 or 100 ng of luteinizing hormone (LH) and 50 ng of epinephrine (EPI), norepinephrine (NOR), dopamine (DOPA), melatonin (MEL), N-acetyl-50H-serotonin (N-acetyl-50H-tryptamine; NacS), serotonin (50H-tryptamine; 5HT) or saline control. 3. EPI, NOR and DOPA decreased baseline release of P4. 4. The magnitude of the response of P4 to LH was depressed when cells were co-incubated with DOPA, EPI and 5HT and stimulated when cells were co-incubated with MEL and NacS. 5. These data indicate that the biogenic amines might modulate ovarian steroidogenesis supplementary to hypothalamic-hypophyseal hormonal mechanisms.     

Effects of reserpine on reproduction and serotonin immunoreactivity in the stable fly Stomoxys calcitrans (L.)

Biogenic amines are known to play critical roles in key insect behaviors such as feeding and reproduction. This study documents the effects of reserpine on mating and egg-laying behaviors of the stable fly, Stomoxys calcitrans (L.) (Diptera: Muscidae), which is one of the most significant biting fly pests affecting cattle. Two sperm staining techniques were adapted successfully to reveal the morphology of stable fly sperm, for the first time, and determine successful mating in females through the assessment of sperm transfer. This approach was also applied to assess sperm transfer by males treated with different doses of reserpine. Mating or sperm transfer did not occur in flies during the first 3 days after emergence. Thereafter, the percentage of females that mated increased with age. Reserpine treatment of males reduced sperm transfer in a dose-dependent manner. Older males were more sensitive to reserpine treatment than younger flies. Reserpine treatment of 5 days old females reduced the number of eggs laid, but had no effect on egg-hatching rates. Results of immunoreactivity (IR) experiments indicated that serotonin in the neuronal processes innervating male testes was completely depleted by reserpine within 5 h after treatment. This effect was transient as the serotonin immunoreactive signal was recovered in 33.3% of the males at 1 day post-treatment and in 94.4% of the flies at 3 days post-treatment. The results of this study concur with previous findings in other insect species and extend our knowledge of the critical roles biogenic amines play in mating and oviposition behaviors of the stable fly. The work could provide a foundation to further characterize the specific roles of individual biogenic amines and their receptors in stable fly reproduction.     

Advances in sodium-ion coupled biogenic amine transporters.

The sodium-ion coupled transporters for 5-hydroxytryptamine (5HT), noradrenaline and dopamine function to reduce extracellular levels of biogenic amines. Over the past fifteen years selective inhibitors of these transport systems have been developed including fluoxetine, citalopram, paroxetine, litoxetine (for 5HT), nisoxetine, desipramine, maprotiline (for noradrenaline) and GBR-12935 (for dopamine). Some of these inhibitors, including drugs selective for noradrenaline transport and particularly those selective for the 5HT transport system are currently widely used in the clinical management of affective disorders. Selective biogenic amine uptake inhibitors have, in addition, provided tools to undertake molecular pharmacological and biochemical studies of their respective transporters. By this means, the rat brain 5HT and dopamine transporters have been identified as polypeptides with relative molecular masses of 73,000 and 80,000, respectively, using affinity-chromatographic purification and photoaffinity-labelling techniques. Recently, the biogenic amine transporters have been cloned and a comparison of their predicted amino acid sequences reveals that these proteins share a considerable degree of similarity with notably 12-13 transmembrane spanning domains. Perspectives for future fundamental and clinical research on biogenic amine transport systems using molecular biological techniques are discussed.     

THE STABILITY OF VITAMIN B6 ACCUMULATION AND PYRIDOXAL KINASE ACTIVITY IN RABBIT BRAIN AND CHOROID PLEXUS

The effects of changes in the concentrations of pyridoxal phosphate and blogenic amines in brain on: (I) pyridoxal kinase (EC 2.7.1.35) activity in brain and choroid plexus; and (2) vitamin B₆ accumulation by brain slices and isolated, intact choroid plexuses were studied. New Zealand white rabbits were treated parenterally with 200 mg/kg pyridoxine-HCl for 3 days or 120 mg/kg 4-deoxypyridoxine HCI or 5 mg/kg reserpine I day before death. After these treatments the mean concentration of pyridoxal phosphate in brain was elevated by 39% by pyridoxine and decreased by 57% by 4-deoxypyridoxine. Reserpine had no effect. However, the ability of brain slices and isolated, intact choroid plexuses from the treated rabbits to accumulate [³H] vitamin B₆ (with [³H]pyridoxine in the medium) was not different from untreated controls. Also, the specific activity of pyridoxal kinase in brain and choroid plexus of treated rabbits was not different from controls. These results show that vitamin B₆ accumulation and pyridoxal kinase activity in brain and choroid plexus are independent of both pyridoxal phosphate and reserpine-sensitive biogenic amine concentrations in brain. In vitro studies with pyridoxal kinase showed that. in both choroid plexus and brain. pyridoxal kinase was a single enzyme with a molecular weight of 43.000 and a K_m , for pyridoxine of 2.0 μM Crude and partially-purified pyridoxal kinase from brain was not inhibited by biogenic amines (1 mM) or pyridoxal phosphate (5 μM). These in vitro data are consistent with the lack of effect of changes in pyridoxal phosphate and biogenic amine concentrations (in brain) on pyridoxal kinase activity in brain in vivo.     

Effect of chronic para-chlorophenylalanine treatment on convulsive-seizure reactions

The effect of chronic para-chlorphenylalanine (PCPA) treatment was investigated in two different seizure models: the pentylenetetrazole (PTX) seizure model in rats and the kindled seizures from rabbit amygdala. Chronic PCPA treatment (21 days) in male albino rats caused a progressive decrease in the 5-hydroxytryptamine (5-HT) brain level between the 1st and the 7th day of PCPA administration. Then the 5-HT level remained low until the end of the experiment. On the background of the low 5-HT level there occurred changes in PTZ convulsive reactions: after the 3rd day of PCPA treatment the convulsive-seizure reactivity was significantly increased and after the 7th, 14th and 21st day the increased seizure reactivity performed only as a tendency, though the 5-HT level was still low. Chronic PCPA treatment (16 days) of rabbits delayed the development of the behavioural kindled seizures. This treatment also reduced the duration of bioelectrical seizures until the 8th day of treatment, especially in the motor cortex. The observed different effect of the chronic PCPA treatment in both seizure models: pentylenetetrazole in rats and kindling in rabbits might be explained by essential differences in the origin and mechanisms of development of the two seizure models.     

Effects of pargyline on hypothalamic biogenic amines and serum prolactin. LH and TSH in male rats.

The time course effects of pargyline on hypothalamic biogenic amines and serum prolactin (PRL), LH and TSH were studied in adult male rats. The rats were killed at intervals of 1–6 hrs after pargyline injection. Hypothalamic dopamine (DA) rose 79% by 1 hr and was 41% above “0” time by 6 hrs. Norepinephrine (NE) increased 31% by 1 hr and remained at about this level through 6 hrs, whereas serotonin (5HT) increased from 42% by 1 hr and to 95% by 6 hrs. Serum PRL LH and TSH fell significantly during the first 2 hrs, but all had returned to pretreatment values by 4 hrs. Serum PRL was about 4-fold above pretreatment values by 6 hrs, but LH and TSH remained at pretreatment levels. Stimulation by pargyline of PRL release was potentiated by Lilly compound 110140, a serotonin reuptake inhibitor, and blocked by parachlorophenylalanine, a serotonin synthesis inhibitor. These results suggest that the inhibitory effects of pargyline on PRL, LH, and TSH release during the first 2 hrs were associated mainly with a rapid increase in DA, and subsequent elevation of PRL release was related to the increase in 5HT. Return of serum LH and TSH to pretreatment levels at 4 and 6 hrs appeared to be associated mainly with the decrease in DA and perhaps to elevated NE levels. These results suggest that changes in relative concentrations of hypothalamic amines are related to differential release of PRL, LH and TSH.     

Hormones in the nucleus. Immunologically demonstrable biogenic amines (serotonin, histamine) in the nucleus of rat peritoneal mast cells

Using 1-ethyl-3(3-dimethyl-aminopropyl)-carbodiimide (EDAC) fixation and immunocytochemical confocal microscopic study, bright serotonin and histamine fluorescence appeared in the nucleus of rat peritoneal mast cells. In case of paraformaldehyde fixation, this was not observed. The phenomenon can be explained by the cross-linking effect of EDAC, which did not allow the efflux of biogenic amines from the nucleus. This means that biogenic amines are present in the nucleus of mast cells, and this is supported by the flow cytometric measurement data of the whole cell. Other hormones studied (triiodothyronine, insulin, and endorphin) were not present in the nucleus. Four pharmaca with biogenic amine-influencing character in the central nervous system were used for studying the relation between the external (surrounding and cytoplasmic) and nuclear biogenic amine content of mast cells. Fluoxetine, a serotonin reuptake inhibitor depleted nuclear as well as cytoplasmic serotonin content. Clorgyline, a MAO-A inhibitor, decreased cytoplasmic serotonin content and weakened nuclear serotonin fluorescence. The tryptophan hydroxylase inhibitor, para-chlorophenylalanine (PCPA), and the mast cell degranulator, Compound 48/80, reduced cytoplasmic serotonin content without influencing nuclear content. Histamine fluorescence was influenced solely by fluoxetine. The results show that nuclear 5-HT content is dependent firstly of serotonin uptake and reuptake. To our knowledge, this is the first exact report on the presence of non-steroid-type-receptor-transported hormones inside the nucleus of a cell.     

Cathepsin C Aggravates Neuroinflammation Involved in Disturbances of Behaviour and Neurochemistry in Acute and Chronic Stress-Induced Murine Model of Depression

Major depression has been interpreted as an inflammatory disease characterized by cell-mediated immune activation, which is generally triggered by various stresses. Microglia has been thought to be the cellular link between inflammation and depression-like behavioural alterations. The expression of cathepsin C (Cat C), a lysosomal proteinase, is predominantly induced in microglia in neuroinflammation. However, little is known about the role of Cat C in pathophysiology of depression. In the present study, Cat C transgenic mice and wild type mice were subjected to an intraperitoneal injection of LPS (0.5 mg/kg) and 6-week unpredictable chronic mild stress (UCMS) exposure to establish acute and chronic stress-induced depression model. We examined and compared the behavioural and proinflammatory cytokine alterations in serum and depression-targeted brain areas of Cat C differentially expressed mice in stress, as well as indoleamine 2,3-dioxygenase (IDO) and 5-hydroxytryptamine (5HT) levels in brain. The results showed that Cat C overexpression (Cat C OE) promoted peripheral and central inflammatory response with significantly increased TNFα, IL-1β and IL-6 in serum, hippocampus and prefrontal cortex, and resultant upregulation of IDO and downregulation of 5HT expression in brain, and thereby aggravated depression-like behaviours accessed by open field test, forced swim test and tail suspension test. In contrast, Cat C knockdown (Cat C KD) partially prevented inflammation, which may help alleviate the symptoms of depression in mice. To the best of our knowledge, we are the first to demonstrate that Cat C aggravates neuroinflammation involved in disturbances of behaviour and neurochemistry in acute and chronic stress-induced murine model of depression.     

Cytochemical localization of Na+/K+-ATPase activity in cochlear strial marginal cells after various catecholamine administrations

Sodium/potassium-activated adenosine triphosphatase (Na+/K+-ATPase) activity in the kidney and brain is high, and is regulated by catecholamines. Na+/K+-ATPase activity is also high in the basolateral infoldings of the strial marginal cells, where it aids in maintaining the characteristic electrolyte composition of the endolymph. To clarify the involvement of humoral control in strial function, particularly the role of catecholamines, the K+-dependent p-nitrophenylphosphatase (K+-NPPase) activity of strial marginal cells was investigated in guinea pigs using a cerium-based cytochemical method. The effects of reserpine, serotonin (5-HT), norepinephrine (NE), epinephrine (EP), both alone and in combination, were studied. High doses of reserpine cause depletion of sympathetic substances. Strial K+-NPPase activity was decreased after reserpine or dopamine treatment, and was increased after 5-HT, NE, and EP treatment. After reserpinization, repeated treatment with 5-HT, NE, or EP led to detectable strial enzyme activity. Thus, exogenous 5-HT, NE, and EP were able to restore strial K+-NPPase activity in the reserpine-treated animals. These results suggested that biogenic amines regulate strial K+-NPPase activity. Thus, the function of the stria vascularis may be regulated by the opposing actions of these catecholamines, and 5-HT.     

Is serotonin a chemical transmitter in the frog taste organ?

By artificially perfusing the frog tongue with serotonin (5HT) and its antagonists, the possibility of 5HT as a chemical transmitter from taste cells to nerve terminals in frog taste organ was examined. Although serotonin creatinine sulfate, when perfused through the lingual artery, produced impulse discharges in the glossopharyngeal nerve, creatinine sulfate elicited a similar response. Neural responses to taste stimuli were depressed by perfusion with 5HT. Among many antiserotonergic drugs perfused through the lingual artery, LSD was the only one which modified responses to taste stimuli. LSD suppressed taste responses to NaCl, CaCl₂ and water, while LSD at a high concentration (10^?5 g/ml) enhanced responses to guinine and HCl. When PCPA (DL-p-chlorophenylalanine) was injected intraperitoneally in conbination with reserpine, the agent did not significantly change taste responses. The above results possibly suggest that 5HT would not be a chemical mediator from taste cells to nerve terminals.     

Serotonin in body fluids: Characterization of human plasmatic and cerebrospinal fluid pools by means of a new HPLC method

A new HPLC technique for the analysis of picomolar amounts of serotonin (5HT) in plasma and cerebrospinal fluid (CSF) is described. Bufotenin is used as internal standard. Detection is achieved electrochemically or fluorimetrically. The detection limit can be estimated as 50 pg 5HT/mL of either fluid (0.3 picomolar). The method is used to characterize a non-particulate pool of 5HT which is clearly distinct of the platelet pool. Administration of parachlorophenylalanine (PCPA) 300 mg/kg to rats leads to a 90% reduction in the plasmatic pool whereas platelet 5HT is only slightly decreased (3rd day after PCPA) or even increased (7th day after PCPA). Human concentration (n=15) of 5HT in plasma is 2.6 ± 0.9 ng/mL (x ± S.D.). The application of the method to CSF of neurological patients reveals 5HT concentrations ranging from 93 to 962 pg/mL.     

Changes in the Content of Brain Biogenic Amine Associated with Early Colony Establishment in the Queen of the Ant, Formica japonica

We examined changes in the content of biogenic amines in the brains of ant queen associated with early colony establishment. In ants, including Formica japonica, winged virgin queens lose their wings following copulation, and then start establishing a colony. Significant changes in brain biogenic amine content in the queen are associated with transition from winged virgin queen to wingless mated queen. The levels of serotonin (5HT), octopamine (OA) and dopamine (DA) decreased significantly in the brain of the queen after starting a colony. On the other hand, tyramine (TA) increased significantly in the brain following colony establishment. Catabolized substances of the biogenic amines in the brain were also measured. The levels of N-acetyloctopamine (Nac-OA) and N-acetyltyramine (Nac-TA) in the brain did not show a significant change after the queen established a colony. However, the levels of N-acetylserotonin (Nac-5HT) in the brain were significantly higher in wingless mated queens than in winged virgin queens, whereas levels of N-acetyldopamine (Nac-DA) in the brain were significantly lower in wingless mated queens than winged virgin queens. These results suggest that serotonergic and octopaminergic systems in the brain of the queen change when the mated queen starts to establish a new colony.     

Cholinergic and serotonergic neural links and the inhibitory effects of hippocampus, lateral amygdala and central gray matter on gonadotropin release.

Effects of electrical stimulation of the hippocampus (HPC), lateral amygdala (1-AMYG) and midbrain central gray matter (CG) on the release of ovulatory gonadotropin were examined using proestrous Wistar rats with or without pretreatment with reserpine, atropine or p-chlorophenylalanine (PCPA) at such dosage that had been confirmed not to block ovulation. Electrical stimulation of the HPC, 1-AMYG or CG under light ether anesthesia just before the critical period prevented a rise in serum LH, FSH and prolactin levels at 18:00. Pretreatment with atropine (200 mg/kg body wt, sc) was effective to abolish this inhibitory effect of the HPC stimulation on the release of LH and FSH, whereas reserpine treatment (1mg/kg body wt, ip) did not affect the effect. The inhibitory effect of the 1-AMYG or CG stimulation on LH and FSH release was abolished by treatment with PCPA (150 mg/kg body wt, ip), while neither atropine nor reserpine had any effect. The inhibitory effect of the HPC stimulation on the release of these hormones was also blocked by PCPA treatment. In regard to the prolactin release, it was inhibited by the stimulation of the HPC, 1-AMYG or CG in both the non-treated rat and in the atropine or PCPA-treated one, while in the reserpine-treated rat it was not inhibited but rather was facilitated by these stimulations. It was assumed that the normal maintenance of both cholinergic and serotonergic neural links for the expression of the HPC inhibition on ovulatory LH, FSH and prolactin secretion and that of serotonergic link for the expression of the 1-AMYG or CG inhibition are needed. The inhibitory action on prolactin release changed into facilitation under the depletion of monoamines, but the mechanism is unknown.