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See detailHuman and Quail Aromatase Activity Is Rapidly and Reversibly Inhibited by Phosphorylating Conditions
Charlier, Thierry ULg; Harada, Nobuhiro; Balthazart, Jacques ULg et al

in Endocrinology (2011), 152(11), 4199-210

Besides their slow genomic actions, estrogens also induce rapid physiological responses. To be functionally relevant, these effects must be associated with rapid changes in local concentrations of ... [more ▼]

Besides their slow genomic actions, estrogens also induce rapid physiological responses. To be functionally relevant, these effects must be associated with rapid changes in local concentrations of estrogens. Rapid changes in aromatase activity (AA) controlled by calcium-dependent phosphorylations of the enzyme can alter in a rapid manner local estrogen concentrations, but so far this mechanism was identified only in the avian (quail) brain. We show here that AA is also rapidly down-regulated by phosphorylating conditions in quail ovary homogenates and in various cell lines transfected with human aromatase (HEK 293, Neuro2A, and C6). Enzymatic activity was also rapidly inhibited after depolarization of aromatase-expressing HEK 293 cells with 100 mm KCl, and activity was fully restored when cells returned to control conditions. Western blot analysis demonstrated that the reduction of enzymatic activity is not due to protein degradation. We next investigated by site-directed mutagenesis the potential implication in the control of AA of specific aromatase residues identified by bioinformatic analysis. Mutation of the amino acids S118, S247, S267, T462, T493, or S497 to alanine, alone or in combination, did not block the rapid inhibition of enzymatic activity induced by phosphorylating conditions, but basal AA was markedly decreased in the S118A mutant. Altogether, these results demonstrate that the rapid inhibition of AA is a widespread and fully reversible process and that phosphorylation of specific residues modulate AA. These processes provide a new general mechanism by which local estrogen concentration can be rapidly altered in the brain and other tissues. [less ▲]

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See detailAcute Stress Differentially Affects Aromatase Activity in Specific Brain Nuclei of Adult Male and Female Quail
Dickens, Molly J; Cornil, Charlotte ULg; Balthazart, Jacques ULg

in Endocrinology (2011), 52(11), 4242-51

The rapid and temporary suppression of reproductive behavior is often assumed to be an important feature of the adaptive acute stress response. However, how this suppression operates at the mechanistic ... [more ▼]

The rapid and temporary suppression of reproductive behavior is often assumed to be an important feature of the adaptive acute stress response. However, how this suppression operates at the mechanistic level is poorly understood.The enzyme aromatase converts testosterone to estradiol in the brain to activate reproductive behavior in male Japanese quail (Coturnix japonica). The discovery of rapid and reversible modification of aromatase activity (AA) provides a potential mechanism for fast, stress induced changes in behavior. We investigated the effects of acute stress on AA in both sexes by measuring enzyme activity in all aromatase-expressing brain nuclei before, during, and after 30 min of acute restraint stress. We show here that acute stress rapidly alters AA in the male and female brain and that these changes are specific to the brain nuclei and sex of the individual. Specifically, acute stress rapidly (5 min) increased AA in the male medial preoptic nucleus, a region controlling male reproductive behavior; in females, a similar increase was also observed, but it appeared delayed (15min) and had smaller amplitude. In the ventromedial and tuberal hypothalamus, regions associated with female reproductive behavior, stress induced a quick and sustained decrease in AA in females, but in males, only a slight increase (ventromedial) or no change (tuberal) in AA was observed. Effects of acute stress on brain estrogen production, therefore, represent one potential way through which stress affects reproduction. [less ▲]

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See detailSEASONAL AND INDIVIDUAL VARIATION IN SINGING BEHAVIOR CORRELATES WITH ALPHA 2-NORADRENERGIC RECEPTOR DENSITY IN BRAIN REGIONS IMPLICATED IN SONG, SEXUAL, AND SOCIAL BEHAVIOR
Heimovics, Sarah A.; Cornil, Charlotte ULg; Hellis, J. M. S. et al

in Neuroscience (2011), 182

In seasonally breeding male songbirds, both the function of song and the stimuli that elicit singing behavior change seasonally. The catecholamine norepinephrine (NE) modulates attention and arousal ... [more ▼]

In seasonally breeding male songbirds, both the function of song and the stimuli that elicit singing behavior change seasonally. The catecholamine norepinephrine (NE) modulates attention and arousal across behavioral states, yet the role of NE in seasonally-appropriate vocal communication has not been well-studied. The present study explored the possibility that seasonal changes in alpha 2-noradrenergic receptors (alpha2-R) within song control regions and brain regions implicated in sexual arousal and social behavior contribute to seasonal changes in song behavior in male European starlings (Sturnus vulgaris). We quantified singing behavior in aviary housed males under spring breeding season conditions and fall conditions. alpha2-R were identified with the selective ligand [3H]RX821002 using autoradiographic methods. The densities of alpha2-R in song control regions (HVC and the robust nucleus of the arcopallium [RA]) and the lateral septum (LS) were lower in Spring Condition males. alpha2-R densities in the caudal portion of the medial preoptic nucleus (POM) related negatively to singing behavior. Testosterone concentrations were highest in Spring Condition males and correlated with alpha2-R in LS and POM. Results link persistent seasonal alterations in the structure or function of male song to seasonal changes in NE alpha2-Rs in HVC, RA, and LS. Individual differences in alpha2-R in the POM may in part explain individual differences in song production irrespective of the context in which a male is singing, perhaps through NE modification of male sexual arousal. [less ▲]

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See detailRapid changes of aromatase activity in discrete brain regions following social interactions
de Bournonville, Catherine ULg; Ball, Gregory, F.; Balthazart, Jacques ULg et al

in Trabajos del Instituto Cajal (2011), LXXXIII

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See detailEffects of social experience on subsequent sexual performance in naïve male Japanese quail (Coturnix japonica)
Cornil, Charlotte ULg; Ball, Gregory

in Hormones & Behavior (2010), 57

On their first sexual encounter, naïve male Japanese quail will attend to and approach a female; they sometimes mount but they do not always copulate. During the second encounter, most males successfully ... [more ▼]

On their first sexual encounter, naïve male Japanese quail will attend to and approach a female; they sometimes mount but they do not always copulate. During the second encounter, most males successfully copulate. Although sexual experience facilitates subsequent sexual interactions, sensory cues provided by females, independent of any sexual encounter, may also enhance sexual performance. To investigate whether previous exposure to a conspecific affects subsequent sexual behavior, we allowed inexperienced males to observe an empty box, or a conspecific consisting of either an experienced female or male for 2.5 min/day on 7 days. Measures of appetitive sexual behavior were recorded during these tests. On day 8, subjects were allowed to copulate with a novel female for 5 min. On the following days, all subjects were repeatedly provided with visual access to a female and allowed to mate. In the pre-copulatory trials males initially exhibited a high frequency of appetitive responses that dissipated with repetition. Pre-copulatory experience also significantly affected motivation to mate with subjects exposed to females copulating more quickly than other subjects. Post-copulatory appetitive behavior also differed between groups: control subjects showed the highest behavioral frequency followed by males exposed to females and finally males exposed to males. These data indicate that pre-copulatory social experience profoundly influences subsequent sexual behavior and probably reproductive success. This experience effect is independent of any hormonal effect (such as one resulting from changes in secretion following different social interactions) given that the subjects were castrates chronically treated with testosterone. [less ▲]

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See detailDiversity of mechanisms involved in aromatase regulation and estrogen action in the brain
Charlier, Thierry ULg; Cornil, Charlotte ULg; Ball, Gregory et al

in Biochimica et Biophysica Acta - General Subjects (2010)

Background In recent years, the mechanisms through which estrogens modulate neuronal physiology, brain morphology, and behavior have proven to be far more complex than previously thought. For example, a ... [more ▼]

Background In recent years, the mechanisms through which estrogens modulate neuronal physiology, brain morphology, and behavior have proven to be far more complex than previously thought. For example, a second nuclear estrogen receptor has been identified, a new family of coregulatory proteins regulating steroid-dependent gene transcriptions was discovered and, finally, it has become clear that estrogens have surprisingly rapid effects based on their actions on cell membranes, which in turn result in the modulation of intracellular signaling cascades. Scope of review This paper presents a selective review of new findings in this area related to work in our laboratories, focusing on the role of estrogens in the activation of male sexual behavior. Two separate topics are considered. We first discuss functions of the steroid receptor coactivator-1 (SRC-1) that has emerged as a key limiting factor for behavioral effects of estradiol. Knocking-down its expression by antisense oligonucleotides drastically inhibits male-typical sexual behaviors. Secondly, we describe rapid regulations of brain estradiol production by calcium-dependent phosphorylations of the aromatase enzyme, themselves under the control of neurotransmitter activity. These rapid changes in estrogen bioavailability have clear behavioral consequences. Increases or decreases in estradiol concentrations respectively obtained by an acute injection of estradiol itself or of an aromatase inhibitor lead within 15–30 min to parallel changes in sexual behavior frequencies. These new controls of estrogen action offer a vast array of possibilities for discrete local controls of estrogen action. They also represent a formidable challenge for neuroendocrinologists trying to obtain an integrated view of brain function in relation to behavior. [less ▲]

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See detailBrain aromatase activity and male sexual behavior
Balthazart, Jacques ULg; Cornil, Charlotte ULg; Charlier, Thierry ULg et al

in Annales d'Endocrinologie (2010), 71

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See detailRapid regulation of aromatase activity and the role of stress
Dickens, Molly; Charlier, Thierry ULg; Cornil, Charlotte ULg et al

Poster (2010)

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See detailIs sexual motivational state linked to dopamine release in the medial preoptic area?
Kleitz-Nelson, Hayley; Dominguez, Juan; Cornil, Charlotte ULg et al

in Behavioral Neuroscience (2010)

The medial preoptic area (mPOA) is a key site for the dopaminergic enhancement of male sexual behavior. Dopamine release increases in the rat mPOA with mating, supporting the critical stimulatory role ... [more ▼]

The medial preoptic area (mPOA) is a key site for the dopaminergic enhancement of male sexual behavior. Dopamine release increases in the rat mPOA with mating, supporting the critical stimulatory role played by preoptic dopamine on male sexual behavior. However, it has been questioned whether dopamine is specifically related to the occurrence of male sexual behavior and not simply involved in general arousal. To address this question, we ask whether dopamine release in the mPOA is linked to the production of male sexual behavior in Japanese quail, a species that exhibits a much shorter temporal pattern of copulation than rats and does not have an intromittent organ, resulting in a very different topography of their sexual response. Extracellular samples from the mPOA of adult sexually experienced male quail were collected every six minutes before, during, and after exposure to a female using in vivo microdialysis and analyzed using HPLC-EC. Extracellular dopamine significantly increased in the presence of a female and returned to baseline after removal of the female. However, subjects who failed to copulate did not display this increased release. These findings indicate that it is not solely the presence of a female that drives dopamine release in males, but how a male responds to her. Further, in subjects that copulated, dopamine release did not change in samples collected during periods of no copulation. Together, these findings support the hypothesis that dopamine action in the mPOA is specifically linked to sexual motivation and not only copulatory behavior or physical arousal. [less ▲]

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See detailTestosterone recruits new aromatase-imunoreactive cells in neonatal quail brain.
Bardet, Sylvia M; Cornil, Charlotte ULg; Balthazart, Jacques ULg

in Neuroreport (2010), 21(5), 376-80

It was shown earlier that, in Japanese quail the mechanism controlling the induction by testosterone of aromatase activity develops between embryonic days 10 and 14. The cellular processes underlying this ... [more ▼]

It was shown earlier that, in Japanese quail the mechanism controlling the induction by testosterone of aromatase activity develops between embryonic days 10 and 14. The cellular processes underlying this activation have, however, not been investigated in detail. Here, we demonstrate that the increase in aromatase activity observed in neonates treated with testosterone propionate between postnatal days 1 and 3 results from the recruitment of additional populations of aromatase-immunoreactive cells that were not expressing the enzyme at detectable levels before. This recruitment concerns all brain nuclei normally expressing the enzyme even if it is more prominent in the ventromedial hypothalamus than in other nuclei. [less ▲]

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See detailBehavioral effects of brain-derived estrogens in birds.
Balthazart, Jacques ULg; Taziaux, Mélanie ULg; Holloway, Kevin et al

in Annals of the New York Academy of Sciences (2009), 1163

In birds as in other vertebrates, estrogens produced in the brain by aromatization of testosterone have widespread effects on behavior. Research conducted with male Japanese quail demonstrates that ... [more ▼]

In birds as in other vertebrates, estrogens produced in the brain by aromatization of testosterone have widespread effects on behavior. Research conducted with male Japanese quail demonstrates that effects of brain estrogens on all aspects of sexual behavior, including appetitive and consummatory components as well as learned aspects, can be divided into two main classes based on their time course. First, estrogens via binding to estrogen receptors regulate the transcription of a variety of genes involved primarily in neurotransmission. These neurochemical effects ultimately result in the activation of male copulatory behavior after a latency of a few days. Correlatively, testosterone and its aromatized metabolites increase the transcription of the aromatase mRNA, resulting in an increased concentration and activity of the enzyme that actually precedes behavioral activation. Second, recent studies with quail demonstrate that brain aromatase activity can also be modulated within minutes by phosphorylation processes regulated by changes in intracellular calcium concentration, such as those associated with glutamatergic neurotransmission. The rapid upregulations or downregulations of brain estrogen concentration (presumably resulting from these changes in aromatase activity) affect, by nongenomic mechanisms with relatively short latencies (frequency increases or decreases respectively within 10-15 min), the expression of male sexual behavior in quail and also in rodents. Brain estrogens thus affect behavior on different time scales by genomic and nongenomic mechanisms similar to those of a hormone or a neurotransmitter. [less ▲]

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See detailEstradiol, a key endocrine signal in the sexual differentiation and activation of reproductive behavior in quail.
Balthazart, Jacques ULg; Cornil, Charlotte ULg; Charlier, Thierry ULg et al

in Journal of Experimental Zoology. Part A, Ecological Genetics and Physiology (2009), 311(5), 323-45

In Japanese quail, estrogen's effects on sexual behavior can be divided into three classes based on the underlying mechanisms and time-course of action and release. During embryonic life, the embryonic ... [more ▼]

In Japanese quail, estrogen's effects on sexual behavior can be divided into three classes based on the underlying mechanisms and time-course of action and release. During embryonic life, the embryonic ovary secretes large amounts of estrogens. In contrast to what is observed in mammals where sexual differentiation essentially proceeds via masculinization of the males, in quail, females are demasculinized by their endogenous ovarian estrogens, an effect that can be blocked by injection of an aromatase inhibitor and mimicked in male embryos by an injection of estradiol. In adulthood, testosterone secreted by the testes is converted into estrogens by the preoptic aromatase. Locally produced estrogens activate male sexual behavior largely through the activation of estrogen receptors resulting in the transcription of a variety of genes, including brain aromatase (genomic effect). Both changes in estrogen production and action are observed within latencies ranging from a few hours to a few days, and are completely reversible. Additionally, brain aromatase activity can be modulated within minutes by calcium-dependent phosphorylations, triggered by variations in glutamatergic neurotransmission. These rapid changes in aromatase activity affect with relatively short latencies (10-15 min) the expression of male sexual behavior in quail and also in mice. Overall, the effects of estrogens on sexual behavior can thus be categorized into three classes: organizational (irreversible genomic action during ontogeny), activational (reversible genomic action during adulthood) and rapid nongenomic effects. Rapid and slower changes in brain aromatase activity match well with the two modes of estrogen action on behavior and provide temporal variations in the estrogens' bioavailability that should be able to support the entire range of established effects for this steroid. [less ▲]

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See detailPresence of aromatase and estrogen receptor alpha in the inner ear of zebra finches.
Noirot, Isabelle ULg; Adler, Henry J; Cornil, Charlotte ULg et al

in Hearing Research (2009)

Sex differences in song behavior and in the neural system controlling song in songbirds are well documented but relatively little is known about sex differences in hearing. We recently demonstrated the ... [more ▼]

Sex differences in song behavior and in the neural system controlling song in songbirds are well documented but relatively little is known about sex differences in hearing. We recently demonstrated the existence of sex differences in auditory brainstem responses in a songbird species, the zebra finch (Taeniopygia guttata). Many sex differences are regulated by sex steroid hormone action either during ontogeny or in adulthood. As a first step to test the possible implication of sex steroids in the control of sex differences in the zebra finch auditory system, we evaluated via immunocytochemistry whether estrogens are produced and act in the zebra finch inner ear. Specifically we examined the distribution of aromatase, the enzyme converting testosterone into an estrogen, and of estrogen receptors of the alpha subtype (ERalpha) in adult zebra finch inner ears. The anatomy of the basilar papillae was visualized by fluorescein-phalloidin, which delineated the actin structure of hair cells and supporting cells at their apical surface. Whole mount preparations of basilar papillae stained by immunocytochemistry revealed in both males and females an abundant aromatase distribution in the cytoplasm of hair cells, while ERalpha was identified in the nuclei of hair cells and of underlying supporting cells. Double labeled preparations confirmed the extensive co-localization of aromatase and ERalpha in the vast majority of the hair cells. These results are consistent with studies on non-avian species, suggesting a role for estrogens in auditory function. These findings are also consistent with the notion that estrogens may contribute to a sex difference in hearing. To our knowledge, this is the first demonstration of the presence of aromatase and of the co-localization of aromatase and ERalpha in the sensory epithelium of the inner ear in any animal model. [less ▲]

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See detailRapid regulation of brain oestrogen synthesis: the behavioural roles of oestrogens and their fates.
Cornil, Charlotte ULg

in Journal of Neuroendocrinology (2009), 21(3), 217-26

Besides their well-known genomic actions, oestrogens also exert effects through the activation of receptors associated with the plasma membrane that are too fast to be mediated by transcriptional ... [more ▼]

Besides their well-known genomic actions, oestrogens also exert effects through the activation of receptors associated with the plasma membrane that are too fast to be mediated by transcriptional activation (nongenomic effects). Although the existence of such rapid effects of oestrogens and their involvement in various biological processes are not in doubt, questions remain about the mechanisms responsible for the rapid modulations of oestrogen production that are required to sustain their nongenomic effects. Recent data indicate that the conversion of androgens into oestrogens in the brain by the enzyme aromatase can be rapidly modulated by conformational changes of the enzyme, thus providing a possible mechanism for rapid controls of the effects of oestrogens on male sexual behaviour. In this review, the data supporting this hypothesis are described. Subsequently, a few unanswered questions are discussed, such as the mechanism of oestrogen inactivation or the potential cellular sites of action of brain-derived oestrogens on male sexual behaviour. [less ▲]

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See detailAre rapid changes in gonadal testosterone release involved in the fast modulation of brain estrogen effects?
Cornil, Charlotte ULg; Stevenson, Tyler J; Ball, Gregory F

in General and Comparative Endocrinology (2009)

Estradiol facilitates the expression of male sexual behavior in Japanese quail within a few minutes. These rapid behavioral effects of estradiol could result from rapid changes in its local production in ... [more ▼]

Estradiol facilitates the expression of male sexual behavior in Japanese quail within a few minutes. These rapid behavioral effects of estradiol could result from rapid changes in its local production in the preoptic area by aromatase, the enzyme converting testosterone into estradiol. Alternatively, aromatase activity may remain constant but fluctuations of local estradiol production could arise from rapid changes in the concentration of the enzymatic substrate, namely testosterone. Rapid increases of circulating testosterone levels have been observed in males of various species following social encounters. Surprisingly, in quail, the interaction with a female seems to result in a decrease in circulating testosterone levels. However, in that study conducted in quail, the samples were collected at intervals longer than the recently observed rapid effects of estradiol on sexual behavior. In the present study we investigated whether plasma testosterone concentrations fluctuate on a shorter time-frame. Eleven male were tested 5 min before and 5, 15 or 30 min after being allowed to have visual access to a female or to copulate with a female for 5 min. Both types of interactions resulted in a significant decline in circulating testosterone levels at latencies as short as 5 min. These data demonstrate that the decrease in testosterone levels is initiated shortly after sexual encounters. Because visual interactions with a female did not result in a rapid increase in testosterone concentrations, these findings rule out the possibility that a rapid rise in circulating testosterone levels participates in the rapid increase in brain estrogen synthesis and its facilitatory effects on copulatory behavior. [less ▲]

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See detailD1-like dopamine receptor density in nuclei involved in social behavior correlates with song in a context-dependent fashion in male European starlings.
Heimovics, Sarah A.; Cornil, Charlotte ULg; Ball, Gregory F. et al

in Neuroscience (2009), 159(3), 962-73

Research in songbirds shows that singing behavior is regulated by both brain areas involved in vocal behavior as well as those involved in social behavior. Interestingly, the precise role of these regions ... [more ▼]

Research in songbirds shows that singing behavior is regulated by both brain areas involved in vocal behavior as well as those involved in social behavior. Interestingly, the precise role of these regions in song can vary as a function of the social, environmental and breeding context. To date, little is known about the neurotransmitters underlying such context-dependent regulation of song. Dopamine (DA) modulates highly motivated, goal-directed behaviors (including sexually motivated song) and emerging data implicate DA in the context-dependent regulation of singing behavior. This study was performed to begin to examine whether differences in DA receptors may underlie, in part, context-dependent differences in song production. We used autoradiographic procedures to label D1-like and D2-like DA receptors to examine the relationship between DA receptor density and singing behavior in multiple contexts in male European starlings (Sturnus vulgaris). Within a breeding context (when testosterone (T) was high), D1-like receptor density in the medial preoptic nucleus (POM) and midbrain central gray (GCt) negatively correlated with song used to attract a female. Additionally in this context, D1-like receptor density in POM, GCt, medial bed nucleus of the stria terminalis (BSTm), and lateral septum (LS) negatively correlated with song likely used to defend a nest box. In contrast, in a non-breeding context (when T was low), D1-like receptor density in POM and LS positively correlated with song used to maintain social flocks. No relationships were identified between song in any context and D2-like receptor densities. Differences in the brain regions and directional relationships between D1-like receptor binding and song suggest that dopaminergic systems play a region and context-specific role in song. These data also suggest that individual variation in singing behavior may, in part, be explained by individual differences in D1-like receptor density in brain regions implicated in social behavior. [less ▲]

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See detailSpecies Differences in the Relative Densities of D1- and D2-Like Dopamine Receptor Subtypes in the Japanese Quail and Rats: An in vitro Quantitative Receptor Autoradiography Study.
Kleitz, H. K.; Cornil, Charlotte ULg; Balthazart, Jacques ULg et al

in Brain, Behavior & Evolution (2009), 73(2), 81-90

Evidence has accumulated that the regulation of male sexual behavior by dopamine might not be the same in Japanese quail (and perhaps all birds) as it is in mammals. For example, the non-selective ... [more ▼]

Evidence has accumulated that the regulation of male sexual behavior by dopamine might not be the same in Japanese quail (and perhaps all birds) as it is in mammals. For example, the non-selective dopamine receptor agonist, apomorphine (APO), facilitates male sexual behavior in rats but inhibits it in quail. Although the general organization of the dopamine system is similar in birds and mammals, it is possible that the relative distribution and/or density of binding sites are different. We therefore compared the relative densities of D1-like and D2-like receptor subtypes in Japanese quail and rats, with the use of in vitro quantitative receptor autoradiography. Brain sections from 8 male rats and 8 male quail were labeled with [(3)H]SCH-23390 and [(3)H]Spiperone. In general we found a systematic species difference in the relative density of D1- vs. D2-like receptors such that the D2/D1 ratio is higher in quail than in rats in areas, known to be important target sites for dopamine action such as striatal regions or the preoptic area, which is also associated with activation of sexual behavior. This difference might explain the variation in the behavioral effectiveness of APO in rats as compared to quail; with a higher relative density of D2-like receptors in quail, a similar dose of APO would be more likely to activate inhibitory processes in quail than in rats. [less ▲]

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See detailDopamine binds to alpha(2)-adrenergic receptors in the song control system of zebra finches (Taeniopygia guttata).
Cornil, Charlotte ULg; Castelino, Christina B; Ball, Gregory F

in Journal of Chemical Neuroanatomy (2008), 35(2), 202-15

A commonly held view is that dopamine exerts its effects via binding to D1- and D2-dopaminergic receptors. However, recent data have emerged supporting the existence of a direct interaction of dopamine ... [more ▼]

A commonly held view is that dopamine exerts its effects via binding to D1- and D2-dopaminergic receptors. However, recent data have emerged supporting the existence of a direct interaction of dopamine with adrenergic but this interaction has been poorly investigated. In this study, the pharmacological basis of possible in vivo interactions between dopamine and alpha(2)-adrenergic receptors was investigated in zebra finches. A binding competition study showed that dopamine displaces the binding of the alpha(2)-adrenergic ligand, [(3)H]RX821002, in the brain. The affinity of dopamine for the adrenergic sites does not differ between the sexes and is 10- to 28-fold lower than that for norepinephrine. To assess the anatomical distribution of this interaction, binding competitions were performed on brain slices incubated in 5nM [(3)H]RX821002 in the absence of any competitor or in the presence of norepinephrine [0.1microM] or dopamine [1microM]. Both norepinephrine and dopamine displaced the binding of the radioligand though to a different extent in most of the regions studied (e.g., area X, the lateral part of the magnocellular nucleus of anterior nidopallium, HVC, arcopallium dorsale, ventral tegmental area and substantia grisea centralis) but not in the robust nucleus of the arcopallium. Together these data provide evidence for a direct interaction between dopamine and adrenergic receptors in songbird brains albeit with regional variation. [less ▲]

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See detailInterplay among catecholamine systems: dopamine binds to alpha2-adrenergic receptors in birds and mammals.
Cornil, Charlotte ULg; Ball, Gregory F

in Journal of Comparative Neurology (The) (2008), 511(5), 610-27

Dopaminergic and adrenergic receptors are G-protein-coupled receptors considered to be different based on their pharmacology and signaling pathways. Some receptor subtypes that are members of one family ... [more ▼]

Dopaminergic and adrenergic receptors are G-protein-coupled receptors considered to be different based on their pharmacology and signaling pathways. Some receptor subtypes that are members of one family are actually closer in phylogenetic terms to some subtypes belonging to the other family, suggesting that the pharmacological specificity among these receptors from different families is not perfect. Indeed, evidence is accumulating that one amine can cross-talk with receptors belonging to the other system. However, most of these observations were collected in vitro using artificial cell models transfected with cloned receptors, so that the occurrence of this phenomenon in vivo as well as its distribution in the central nervous system is not known. In this study the pharmacological basis of possible in vivo interactions between dopamine and alpha(2)-adrenergic receptors was investigated in quail, zebra finches, and rats. Binding competitions showed that dopamine displaces the binding of the selective alpha(2)-adrenergic ligand, [(3)H]RX821002, in the brain of the three species with an affinity approximately 10-28-fold lower than that of norepinephrine. Dopamine also displaces with an affinity 3-fold lower than norepinephrine the binding of [(3)H]RX821002 to human alpha(h2A)-adrenergic receptors expressed in Sf9 cells. The anatomical distribution of this interaction was assessed in brain slices of quail and rat based on autoradiographic methods. Both norepinephrine and dopamine significantly displace [(3)H]RX821002 binding in all brain nuclei considered. Together, these data provide evidence for an interaction between the dopaminergic and noradrenergic systems in the vertebrate brain, albeit with species variations. [less ▲]

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