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Pertti Panula - One of the best experts on this subject based on the ideXlab platform.
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embryonic exposure to valproic acid affects the Histaminergic system and the social behaviour of adult zebrafish danio rerio
British Journal of Pharmacology, 2018Co-Authors: Diego Baronio, Maria Sundvik, Henri A J Puttonen, Svetlana Semenova, Essi Lehtonen, Pertti PanulaAbstract:BACKGROUND AND PURPOSE: Histamine modulates several behaviours and physiological functions, and its deficiency is associated with neuropsychiatric disorders. Gestational intake of valproic acid (VPA) is linked to autism spectrum disorder (ASD), characterized by impaired sociability and stereotypies. VPA effects on the neurochemistry and functional morphology of the Histaminergic system in ASD are unclear. Zebrafish are highly social, and given the similarities between zebrafish and human neurotransmitter systems, we have studied the effects of VPA on histamine in zebrafish. EXPERIMENTAL APPROACH: Histaminergic, dopaminergic and noradrenergic systems of larval and adult zebrafish exposed to VPA from the end of gastrulation until neural tube formation were studied using HPLC, quantitative PCR, immunocytochemistry and in situ hybridization. Sociability, dark-flash response and locomotion were also studied. KEY RESULTS: Zebrafish larvae exposed to VPA showed decreased locomotion and an abnormal dark-flash response. Additionally, a reduced number of Histaminergic neurons, low histamine and altered mRNA expression of key genes of the monoaminergic systems were also detected. The reduced mRNA expression of genes of the studied systems persisted until adulthood. Furthermore, adult VPA-exposed animals presented lower brain levels of noradrenaline and 3,4-dihydroxyphenylacetic acid, along with impaired sociability. CONCLUSIONS AND IMPLICATIONS: VPA exposure in early development causes molecular and neurochemical alterations in zebrafish, which persist into adulthood and accompany impaired sociability. These findings will highlight the possible involvement of the Histaminergic system in outcomes related to neuropsychiatric disorders. Furthermore, it supports zebrafish as a tool to investigate mechanisms underlying these disorders.
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storage of neural histamine and Histaminergic neurotransmission is vmat2 dependent in the zebrafish
Scientific Reports, 2017Co-Authors: Henri A J Puttonen, Maria Sundvik, Svetlana Semenova, Pertti PanulaAbstract:Monoaminergic neurotransmission is greatly dependent on the function of the vesicular monoamine transporter VMAT2, which is responsible for loading monoamines into secretory vesicles. The role of VMAT2 in Histaminergic neurotransmission is poorly understood. We studied the structure and function of the Histaminergic system in larval zebrafish following inhibition of VMAT2 function by reserpine. We found that reserpine treatment greatly reduced histamine immunoreactivity in neurons and an almost total disappearance of histamine-containing nerve fibers in the dorsal telencephalon and habenula, the most densely innervated targets of the hypothalamic histamine neurons. The reserpine treated larvae had an impaired histamine-dependent dark-induced flash response seen during the first second after onset of darkness, implying that function of the Histaminergic network is VMAT2 dependent. Levels of histamine and other monoamines were decreased in reserpine treated animals. This study provides conclusive evidence of the relevance of VMAT2 in Histaminergic neurotransmission, further implying that the storage and release mechanism of neural histamine is comparable to that of other monoamines. Our results also reveal potential new insights about the roles of monoaminergic neurotransmitters in the regulation of locomotion increase during adaptation to darkness.
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interactions of the orexin hypocretin neurones and the Histaminergic system
Acta Physiologica, 2015Co-Authors: Maria Sundvik, Pertti PanulaAbstract:Histaminergic and orexin/hypocretin systems are components in the brain wake-promoting system. Both are affected in the sleep disorder narcolepsy, but the role of histamine in narcolepsy is unclear. The Histaminergic neurones are activated by the orexin/hypocretin system in rodents, and the development of the orexin/hypocretin neurones is bidirectionally regulated by the Histaminergic system in zebrafish. This review summarizes the current knowledge of the interactions of these two systems in normal and pathological conditions in humans and different animal models.
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Interactions of the orexin/hypocretin neurones and the Histaminergic system
Acta Physiologica, 2014Co-Authors: Maria Sundvik, Pertti PanulaAbstract:Histaminergic and orexin/hypocretin systems are components in the brain wake-promoting system. Both are affected in the sleep disorder narcolepsy, but the role of histamine in narcolepsy is unclear. The Histaminergic neurones are activated by the orexin/hypocretin system in rodents, and the development of the orexin/hypocretin neurones is bidirectionally regulated by the Histaminergic system in zebrafish. This review summarizes the current knowledge of the interactions of these two systems in normal and pathological conditions in humans and different animal models.
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organization of the Histaminergic system in adult zebrafish danio rerio brain neuron number location and cotransmitters
The Journal of Comparative Neurology, 2012Co-Authors: Maria Sundvik, Pertti PanulaAbstract:Histamine is an essential factor in the ascending arousal system (AAS) during motivated behaviors. Histamine and hypocretin/orexin (hcrt) are proposed to be responsible for different aspects of arousal and wakefulness, histamine mainly for cognitive and motivated behaviors. In this study we visualized the entire Histaminergic neuron population in adult male and female zebrafish brain and quantified the Histaminergic neuron numbers. There were 40–45 Histaminergic neurons in both male and female zebrafish brain. Further, we identified cotransmitters of Histaminergic neurons in the ventrocaudal hypothalamus, i.e., around the posterior recess (PR) in adult zebrafish. Galanin, γ-aminobutyric acid (GABA), and thyrotropin-releasing hormone (TRH) were colocalized with histamine in some but not all neurons, a result that was verified by intracerebroventricular injections of colchicine into adult zebrafish. Fibers immunoreactive (ir) for galanin, GABA, TRH, or methionine-enkephalin (mENK) were dense in the ventrocaudal hypothalamus around the Histaminergic neurons. In histamine-ir fibers TRH and galanin immunoreactivities were also detected in the ventral telencephalon. All these neurotransmitters are involved in maintaining the equilibrium of the sleep–wake state. Our results are in accordance with results from rats, further supporting the use of zebrafish as a tool to study molecular mechanisms underlying complex behaviors. J. Comp. Neurol. 520:3827–3845, 2012. © 2012 Wiley Periodicals, Inc.
Maria Sundvik - One of the best experts on this subject based on the ideXlab platform.
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embryonic exposure to valproic acid affects the Histaminergic system and the social behaviour of adult zebrafish danio rerio
British Journal of Pharmacology, 2018Co-Authors: Diego Baronio, Maria Sundvik, Henri A J Puttonen, Svetlana Semenova, Essi Lehtonen, Pertti PanulaAbstract:BACKGROUND AND PURPOSE: Histamine modulates several behaviours and physiological functions, and its deficiency is associated with neuropsychiatric disorders. Gestational intake of valproic acid (VPA) is linked to autism spectrum disorder (ASD), characterized by impaired sociability and stereotypies. VPA effects on the neurochemistry and functional morphology of the Histaminergic system in ASD are unclear. Zebrafish are highly social, and given the similarities between zebrafish and human neurotransmitter systems, we have studied the effects of VPA on histamine in zebrafish. EXPERIMENTAL APPROACH: Histaminergic, dopaminergic and noradrenergic systems of larval and adult zebrafish exposed to VPA from the end of gastrulation until neural tube formation were studied using HPLC, quantitative PCR, immunocytochemistry and in situ hybridization. Sociability, dark-flash response and locomotion were also studied. KEY RESULTS: Zebrafish larvae exposed to VPA showed decreased locomotion and an abnormal dark-flash response. Additionally, a reduced number of Histaminergic neurons, low histamine and altered mRNA expression of key genes of the monoaminergic systems were also detected. The reduced mRNA expression of genes of the studied systems persisted until adulthood. Furthermore, adult VPA-exposed animals presented lower brain levels of noradrenaline and 3,4-dihydroxyphenylacetic acid, along with impaired sociability. CONCLUSIONS AND IMPLICATIONS: VPA exposure in early development causes molecular and neurochemical alterations in zebrafish, which persist into adulthood and accompany impaired sociability. These findings will highlight the possible involvement of the Histaminergic system in outcomes related to neuropsychiatric disorders. Furthermore, it supports zebrafish as a tool to investigate mechanisms underlying these disorders.
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storage of neural histamine and Histaminergic neurotransmission is vmat2 dependent in the zebrafish
Scientific Reports, 2017Co-Authors: Henri A J Puttonen, Maria Sundvik, Svetlana Semenova, Pertti PanulaAbstract:Monoaminergic neurotransmission is greatly dependent on the function of the vesicular monoamine transporter VMAT2, which is responsible for loading monoamines into secretory vesicles. The role of VMAT2 in Histaminergic neurotransmission is poorly understood. We studied the structure and function of the Histaminergic system in larval zebrafish following inhibition of VMAT2 function by reserpine. We found that reserpine treatment greatly reduced histamine immunoreactivity in neurons and an almost total disappearance of histamine-containing nerve fibers in the dorsal telencephalon and habenula, the most densely innervated targets of the hypothalamic histamine neurons. The reserpine treated larvae had an impaired histamine-dependent dark-induced flash response seen during the first second after onset of darkness, implying that function of the Histaminergic network is VMAT2 dependent. Levels of histamine and other monoamines were decreased in reserpine treated animals. This study provides conclusive evidence of the relevance of VMAT2 in Histaminergic neurotransmission, further implying that the storage and release mechanism of neural histamine is comparable to that of other monoamines. Our results also reveal potential new insights about the roles of monoaminergic neurotransmitters in the regulation of locomotion increase during adaptation to darkness.
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interactions of the orexin hypocretin neurones and the Histaminergic system
Acta Physiologica, 2015Co-Authors: Maria Sundvik, Pertti PanulaAbstract:Histaminergic and orexin/hypocretin systems are components in the brain wake-promoting system. Both are affected in the sleep disorder narcolepsy, but the role of histamine in narcolepsy is unclear. The Histaminergic neurones are activated by the orexin/hypocretin system in rodents, and the development of the orexin/hypocretin neurones is bidirectionally regulated by the Histaminergic system in zebrafish. This review summarizes the current knowledge of the interactions of these two systems in normal and pathological conditions in humans and different animal models.
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Interactions of the orexin/hypocretin neurones and the Histaminergic system
Acta Physiologica, 2014Co-Authors: Maria Sundvik, Pertti PanulaAbstract:Histaminergic and orexin/hypocretin systems are components in the brain wake-promoting system. Both are affected in the sleep disorder narcolepsy, but the role of histamine in narcolepsy is unclear. The Histaminergic neurones are activated by the orexin/hypocretin system in rodents, and the development of the orexin/hypocretin neurones is bidirectionally regulated by the Histaminergic system in zebrafish. This review summarizes the current knowledge of the interactions of these two systems in normal and pathological conditions in humans and different animal models.
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organization of the Histaminergic system in adult zebrafish danio rerio brain neuron number location and cotransmitters
The Journal of Comparative Neurology, 2012Co-Authors: Maria Sundvik, Pertti PanulaAbstract:Histamine is an essential factor in the ascending arousal system (AAS) during motivated behaviors. Histamine and hypocretin/orexin (hcrt) are proposed to be responsible for different aspects of arousal and wakefulness, histamine mainly for cognitive and motivated behaviors. In this study we visualized the entire Histaminergic neuron population in adult male and female zebrafish brain and quantified the Histaminergic neuron numbers. There were 40–45 Histaminergic neurons in both male and female zebrafish brain. Further, we identified cotransmitters of Histaminergic neurons in the ventrocaudal hypothalamus, i.e., around the posterior recess (PR) in adult zebrafish. Galanin, γ-aminobutyric acid (GABA), and thyrotropin-releasing hormone (TRH) were colocalized with histamine in some but not all neurons, a result that was verified by intracerebroventricular injections of colchicine into adult zebrafish. Fibers immunoreactive (ir) for galanin, GABA, TRH, or methionine-enkephalin (mENK) were dense in the ventrocaudal hypothalamus around the Histaminergic neurons. In histamine-ir fibers TRH and galanin immunoreactivities were also detected in the ventral telencephalon. All these neurotransmitters are involved in maintaining the equilibrium of the sleep–wake state. Our results are in accordance with results from rats, further supporting the use of zebrafish as a tool to study molecular mechanisms underlying complex behaviors. J. Comp. Neurol. 520:3827–3845, 2012. © 2012 Wiley Periodicals, Inc.
Atsushi Yamatodani - One of the best experts on this subject based on the ideXlab platform.
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Action of modafinil through Histaminergic and orexinergic neurons.
Vitamins and Hormones Series, 2012Co-Authors: Tomoko Ishizuka, Tomotaka Murotani, Atsushi YamatodaniAbstract:Abstract Modafinil is a wake-promoting drug used for the treatment of excessive daytime sleepiness due to narcolepsy as well as excessive sleepiness associated with obstructive sleep apnea and shift work disorder. Although the wake-promoting effect of modafinil is expressed through the dopaminergic and the norepinephrinergic systems similar to that of classical psychostimulants, the mechanism of action is distinct from those compounds in terms of the involvement of the Histaminergic and the orexinergic systems. Modafinil activates the Histaminergic system in an indirect manner, presumably via attenuation of the inhibitory GABAergic input to the Histaminergic neurons. The orexinergic system controls arousal through the Histaminergic system, and the modafinil-induced increment of histamine release is abolished in orexin neuron-ablated mice, suggesting that modafinil increases Histaminergic tone via orexinergic neurons. Clinical and experimental investigations have suggested less importance of the orexinergic system in the wake-promoting effect of modafinil, but the orexinergic system is considered to be involved in modafinil-induced alertness or synaptic plasticity.
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Integrative role of the Histaminergic system in feeding and taste perception
Frontiers in Systems Neuroscience, 2012Co-Authors: Tomoko Ishizuka, Atsushi YamatodaniAbstract:Feeding behavior is regulated by a complex interplay of many endogenous substances, such as peptides and neurotransmitters in the central nervous system. Histamine is a neurotransmitter which expresses an anorectic effect on food intake via histamine H1 receptors. The Histaminergic system exists downstream of leptin, a satiety factor secreted from white adipose tissue. Because direct stimulation of the Histaminergic system by histamine H3-inverse agonists or antagonists can normalize the obese phenotype in which animal models with exogenous leptin resistance, which resembles human obesity, the potential roles of histamine H3 receptors as a therapeutic target now draw attention. Histaminergic activity is enhanced during feeding, and an oral somatic sensation is thought to affect Histaminergic activity while blood glucose levels do not. In addition, gustatory information can modulate Histaminergic activity by two mechanisms: by physiological excitation of the chorda tympani nerve, one of the taste nerves, and by emotions elicited by taste perception, i.e. taste palatability. Particularly, aversive and hazardous taste stimuli tonically facilitate Histaminergic activity, suggesting that the Histaminergic system is involved in the response to harmful stimuli. Together with recent findings, it is postulated that the Histaminergic system responds to both mechanical and chemical sensory input from the oral cavity during feeding and is exerted as a part of the danger response system.
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modanifil activates the Histaminergic system through the orexinergic neurons
Neuroscience Letters, 2010Co-Authors: Tomoko Ishizuka, Tomotaka Murotani, Atsushi YamatodaniAbstract:Modafinil is a drug used to treat hypersomnolence of narcolepsy. We previously reported that modafinil increases hypothalamic histamine release in rats but did not increase locomotor activity in histamine-depleted mice, suggesting that modafinil-induced locomotor activity involves the Histaminergic system. Modafinil is also thought to express its effect through the orexinergic neurons, and orexin increases hypothalamic histamine release. These findings led us to investigate whether modafinil activates the Histaminergic system via the orexinergic system. In the present study, we performed in vivo microdialysis and c-Fos immunohistochemistry to investigate whether the orexinergic system mediates the activation of the Histaminergic system by modafinil using orexin neuron-deficient mice. Two hours after the injection, modafinil (150 mg/kg) caused a significant increase of histamine release compared to the basal release in wild type mice. However, modafinil had no effect on the histamine release in orexin neuron-deficient mice. By immunohistochemical study, we found that there was no neuronal activation in the tuberomammillary nucleus where the cell bodies of the Histaminergic neurons exclusively exist in orexin neuron-deficient mice. These findings indicate that modafinil-induced increment of histamine release requires intact orexinergic neurons.
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a role of the Histaminergic system for the control of feeding by orexigenic peptides
Physiology & Behavior, 2006Co-Authors: Tomoko Ishizuka, Sachiko Nomura, Hiroshi Hosoda, Kenji Kangawa, Takeshi Watanabe, Atsushi YamatodaniAbstract:Abstract A considerable number of neuropeptides are involved in the hypothalamic regulation of feeding behavior. We previously reported that leptin, the ob gene product, expressed its anorectic effect though the Histaminergic system via histamine H 1 receptors. However, the interactions among the orexigenic neuropeptides, such as orexin-A, neuropeptide Y (NPY), and ghrelin, and the Histaminergic system have not yet been clarified. In this study, we investigated the effect of the neuropeptides on the hypothalamic histamine release in rats, and on food intake and locomotor activity in H 1 -receptor knockout (H1R-KO) mice. Orexin-A increased the histamine release and locomotor activity, but not food intake, suggesting that the Histaminergic system participates in arousal rather than feeding by orexin-A. NPY also increased histamine release, but its effect was not immediate. NPY-injected H1R-KO mice consumed more food than the wild-type mice; thus, the Histaminergic system may act as a feedback factor downstream of NPY. Ghrelin did not affect histamine release, and it increased food intake, even in H1R-KO mice. Thus, ghrelin expresses its action in a histamine-independent manner.
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Histaminergic neuron system: morphological features and possible functions.
Agents and actions, 1991Co-Authors: Hiroshi Wada, Naoyuki Inagaki, Nobuko Itowi, Atsushi YamatodaniAbstract:: The Histaminergic neuron systems in rat brain have been identified by immunocytochemical techniques using antibodies against histidine decarboxylase or histamine itself. Here, the details of the distribution of the Histaminergic neuron networks are presented. Judging from the widespread distribution of the nervous system, it is postulated that the Histaminergic neuron system is involved in various brain functions. Some functions, including the circadian rhythms, sleep-arousal cycles, drinking, feeding, thermoregulation, and neuroendocrine controls which were elucidated by administration of alpha-fluoromethylhistidine, a suicide substrate for histidine decarboxylase, are discussed here, although the true functions are still under investigations.
Csaba Fekete - One of the best experts on this subject based on the ideXlab platform.
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thyrotropin releasing hormone containing axons innervate Histaminergic neurons in the tuberomammillary nucleus
Brain Research, 2012Co-Authors: Anna Sarvari, Erzsebet Farkas, Gyorgyi Zseli, Tamas Fuzesi, Ronald M. Lechan, Andrea Kadar, Csaba FeketeAbstract:Abstract Recent studies indicate that the effect of thyrotropin-releasing hormone (TRH) on the regulation of food intake may be mediated by Histaminergic neurons. To elucidate the anatomical basis for a functional relationship between TRH- and histamine-synthesizing neuronal systems, double-labeling immunocytochemistry was performed on the tuberomammillary nucleus (TMN) of rats, the exclusive location of Histaminergic neurons. TRH-immunoreactive (IR) innervation of the Histaminergic neurons were detected in all five subnuclei (E1–5) of the TMN, but was most prominent in the E4 and E5 subnuclei where 100% of the histamine-IR neurons were contacted. The number of TRH-IR varicosities in contact with histamine-IR neurons was also greatest in the E4 and E5 subnuclei, averaging 27.0±1.2 in E4 and 7.9±0.5 in E5. Somewhat fewer histamine-IR neurons were juxtaposed by TRH-IR varicosities in E2 and E3 and contacted by 6.3±0.2 and 6.8±0.2 varicosities/innervated cell, respectively. The number of juxtapositions of TRH-IR axon varicosities with histamine-IR neurons was the lowest in the E1 subnucleus (85.7±0.9%; 4.0±0.2 varicosities/innervated cell). Ultrastructural analysis demonstrated that TRH-IR axons established both asymmetric and symmetric type synapses on the perikaryon and dendrites of the histamine-IR neurons, although the majority of synapses were asymmetric type. These data demonstrate that TRH neurons heavily innervate Histaminergic neurons in all subdivisions of the TMN, with the densest innervation in the E4 and E5 subdivisions, and are likely to exert activating effects.
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histamine immunoreactive neurons of the tuberomammillary nucleus are innervated by α melanocyte stimulating hormone containing axons generation of a new histamine antiserum for ultrastructural studies
Brain Research, 2003Co-Authors: Csaba Fekete, Zsolt LipositsAbstract:Leptin regulates the release of histamine in the hypothalamus, however, the Histaminergic neurons contain few leptin receptors. To reveal that α-melanocyte stimulating hormone (α-MSH)-containing neurons of the arcuate nucleus may mediate the effects of leptin to the Histaminergic neurons, we studied the putative innervation of histamine-immunoreactive (IR) neurons by α-MSH-containing axons using double-labeling immunocytochemistry. In order to analyze the relationship of α-MSH- and histamine-IR elements, we also generated an antiserum against histamine that is compatible with acrolein-based fixatives commonly used for immuno-electron microscopic studies. The apposition of α-MSH-IR axons to Histaminergic neurons was observed in all five subnuclei of the tuberomammillary nucleus. Both axo-somatic and axo-dendritic contacts were found. At the ultrastructural level, silver-intensified colloidal gold particles identified the Histaminergic neurons, whose ultrastructure was well preserved after fixation with acrolein demonstrating that the new antiserum is a useful tool for the ultrastructural examination of the Histaminergic system. The histamine-IR cells received synaptic inputs from α-MSH-IR axon terminals visualized by diaminobenzidine. These data indicate that α-MSH-synthesizing neurons innervate Histaminergic neurons in the tuberomammillary nucleus and may relay the hormonal influence of leptin to the Histaminergic system.
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Histamine-immunoreactive neurons of the tuberomammillary nucleus are innervated by alpha-melanocyte stimulating hormone-containing axons. Generation of a new histamine antiserum for ultrastructural studies.
Brain research, 2003Co-Authors: Csaba Fekete, Zsolt LipositsAbstract:Leptin regulates the release of histamine in the hypothalamus, however, the Histaminergic neurons contain few leptin receptors. To reveal that alpha-melanocyte stimulating hormone (alpha-MSH)-containing neurons of the arcuate nucleus may mediate the effects of leptin to the Histaminergic neurons, we studied the putative innervation of histamine-immunoreactive (IR) neurons by alpha-MSH-containing axons using double-labeling immunocytochemistry. In order to analyze the relationship of alpha-MSH- and histamine-IR elements, we also generated an antiserum against histamine that is compatible with acrolein-based fixatives commonly used for immuno-electron microscopic studies. The apposition of alpha-MSH-IR axons to Histaminergic neurons was observed in all five subnuclei of the tuberomammillary nucleus. Both axo-somatic and axo-dendritic contacts were found. At the ultrastructural level, silver-intensified colloidal gold particles identified the Histaminergic neurons, whose ultrastructure was well preserved after fixation with acrolein demonstrating that the new antiserum is a useful tool for the ultrastructural examination of the Histaminergic system. The histamine-IR cells received synaptic inputs from alpha-MSH-IR axon terminals visualized by diaminobenzidine. These data indicate that alpha-MSH-synthesizing neurons innervate Histaminergic neurons in the tuberomammillary nucleus and may relay the hormonal influence of leptin to the Histaminergic system.
K Saeki - One of the best experts on this subject based on the ideXlab platform.
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Effect of minute amounts of [D-Ala2,MePhe4,Gly(ol)5]enkephalin injected into the tuberomammillary nucleus of rats on histamine release from the cerebral cortex.
Neuroscience letters, 1995Co-Authors: T Chikai, K SaekiAbstract:[D-Ala2,MePhe4,Gly(ol)5]enkephalin (DAGO) (10 ng/0.5 microliters saline solution) injected into the tuberomammillary nucleus (TM) of rats in minute amounts decreased the amount of histamine released to approximately 50% of the basal value on measurements taken 20-40 min after administration. This effect of DAGO was inhibited by the simultaneous microinjection of naloxone (320 ng). These results may be explained in two ways. The first is that the stimulation of mu-receptors results in the inhibition of Histaminergic cell bodies. The second is that the somatodendritic release of histamine was increased by the stimulation of mu-receptors and as a result of increased histamine concentration in TM, many Histaminergic neurons may be inhibited through the stimulation of H3-receptors. Further studies are necessary regarding the influence of mu-agonists on various cellular sites of Histaminergic neurons.
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effect of minute amounts of d ala2 mephe4 gly ol 5 enkephalin injected into the tuberomammillary nucleus of rats on histamine release from the cerebral cortex
Neuroscience Letters, 1995Co-Authors: T Chikai, K SaekiAbstract:Abstract [ d -Ala 2 ,MePhe 4 ,Gly(ol) 5 ]enkephalin (DAGO) (10 ng/0.5 μ1 saline solution) injected into the tuberomammillary nucleus (TM) of rats in minute amounts decreased the amount of histamine released to approximately 50% of the basal value on measurements taken 20–40 min after administration. This effect of DAGO was inhibited by the simultaneous microinjection of naloxone (320 ng). These results may be explained in two ways. The first is that the stimulation of μ-receptors results in the inhibition of Histaminergic cell bodies. The second is that the somatodendritic release of histamine was increased by the stimulation of μ-receptors and as a result of increased histamine concentration in TM, many Histaminergic neurons may be inhibited through the stimulation of H 3 -receptors. Further studies are necessary regarding the influence of μ-agonists on various cellular sites of Histaminergic neurons.