RESUMEN
GABAA receptor activation augments electrically-stimulated release of norepinephrine (NE) from rat brain slices. Because this effect is not observed in synaptoneurosomes, GABA probably acts on inhibitory interneurons to disinhibit NE release. To determine whether opioids or adenosine influence GABA-augmented NE release, hypothalamic and cortical slices from female rats were superfused with GABA or vehicle in the presence and absence of 10 microM morphine or 100 microM adenosine. GABA augments [3H]NE release in the cortex and hypothalamus. Morphine alone has no effect on [3H]NE release, but attenuates GABA augmentation of [3H]NE release in both brain regions. Adenosine alone modestly inhibits [3H]NE release in the cortex, but not in the hypothalamus. Adenosine inhibits GABA-augmented [3H]NE release in both brain regions. The general protein kinase inhibitor H-7, augments [3H]NE release in both brain regions and may have additive effects with GABA in cortical slices. These results implicate opioid and adenosine interneurons and possibly protein kinases in regulating GABAergic influences on NE transmission.
Asunto(s)
Adenosina/farmacología , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Narcóticos/farmacología , Norepinefrina/metabolismo , Ácido gamma-Aminobutírico/farmacología , 1-(5-Isoquinolinesulfonil)-2-Metilpiperazina/farmacología , Animales , Estimulación Eléctrica , Inhibidores Enzimáticos/farmacología , Femenino , Lóbulo Frontal/efectos de los fármacos , Lóbulo Frontal/metabolismo , Hipotálamo/efectos de los fármacos , Hipotálamo/metabolismo , Técnicas In Vitro , Norepinefrina/antagonistas & inhibidores , Lóbulo Parietal/efectos de los fármacos , Lóbulo Parietal/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
This review focuses on findings from our laboratory regarding mechanisms by which the ovarian steroid hormones, estradiol (E2) and progesterone (P), act in the hypothalamus (HYP) to regulate the expression of lordosis, an important component of female reproductive behavior in rats and many other species. The first section summarizes recent work suggesting that cGMP, perhaps via P-receptor activation, may be an intracellular mediator of the facilitatory actions of a variety of hormones and neurotransmitters on lordosis behavior in E2-primed rats. In the second section, we focus on E2 and P regulation of norepinephrine (NE) neurotransmission in the HYP. We review evidence that ovarian hormones act both peripherally and centrally to determine whether NE is released in the HYP in response to copulatory stimuli. We also suggest that the steroid milieu determines the cellular responses of hypothalamic neurons to released NE, favoring the activation of pathways implicated in the facilitation of both lordosis behavior and the preovulatory gonadotropin surge. It is likely that E2 and P have similar actions on other neurotransmitter and neuromodulator systems, thereby maximizing the probability that females are sexually receptive during the periovulatory period.
Asunto(s)
Estradiol/fisiología , Neurotransmisores/fisiología , Progesterona/fisiología , Conducta Sexual Animal/fisiología , Conducta Sexual/fisiología , Animales , Mapeo Encefálico , Femenino , Humanos , Hipotálamo/fisiología , RatasRESUMEN
Activation of alpha1-adrenergic receptors has been linked to the control of blood pressure, neuroendocrine secretion, reproductive behavior and mood. The present study describes the distribution of alpha1B-adrenergic receptor immunoreactivity in female rat brain regions involved in stress and neuroendocrine function. The pattern of immunolabeling seen resembles that obtained in previous in situ hybridization studies. Several hypothalamic areas that control pituitary function showed intense fiber and/or cell immunolabeling, including the paraventricular nucleus of the hypothalamus, the supraoptic nucleus, and the median eminence. Some regions such as the arcuate nucleus, the median eminence, and dorsal hypothalamus exhibit intense labeling of axonal varicosities, while other regions exhibit only perikarya immunolabeling. alpha1B-adrenergic receptor immunoreactivity was also observed in large pyramidal neurons of layer V of the cerebral cortex, the frontal cortex showing a particularly strong immunoreactivity. Virtually all thalamic regions were labeled, especially the lateral and ventral areas. In addition, labeled cells were present in hippocampus, the medial septum, the horizontal and vertical limbs of the diagonal band of Broca, and the caudate putamen. Finally, some midbrain and hindbrain regions important for motor function were immunoreactive. Because ligands specific for alpha1-adrenergic receptor subtypes are not available, the present immunocytochemical study not only addresses the subcellular and regional distribution of alpha1B-adrenergic receptors but may also provide clues about receptor subtype-specific function.
Asunto(s)
Encéfalo/metabolismo , Sistemas Neurosecretores/fisiología , Receptores Adrenérgicos alfa 1/metabolismo , Estrés Fisiológico/metabolismo , Animales , Encéfalo/fisiología , Femenino , Inmunohistoquímica , Ratas , Ratas Sprague-DawleyRESUMEN
GABAA receptor activation augments stimulated release of 3H-norepinephrine (NE) in brain slices from female rats. This effect is not blocked by acetazolamide or MK-801, indicating that permeability of the GABAA chloride channel to bicarbonate ions and NMDA receptor activation do not mediate GABA-induced NE release. Furthermore, GABA augments 3H-NE release from slices, but not from isolated nerve terminals (synaptosomes), indicating that interneurons mediate GABA effects on 3H-NE release.
Asunto(s)
Interneuronas/fisiología , Norepinefrina/metabolismo , Ácido gamma-Aminobutírico/fisiología , Acetazolamida/farmacología , Animales , Anticonvulsivantes/farmacología , Agonistas de Aminoácidos Excitadores/farmacología , Femenino , Lóbulo Frontal/citología , Lóbulo Frontal/metabolismo , Interneuronas/química , Interneuronas/efectos de los fármacos , N-Metilaspartato/farmacología , Técnicas de Cultivo de Órganos , Área Preóptica/citología , Área Preóptica/metabolismo , Ratas , Ratas Sprague-Dawley , Receptores de GABA-A/fisiología , Sinaptosomas/efectos de los fármacos , Sinaptosomas/metabolismoRESUMEN
These studies examined the regulation by GABA of norepinephrine release from hypothalamus, preoptic area and frontal cortex. Using superfused brain slices from female rats, we show that 100 microM GABA enhances both basal and electrically stimulated release of 3H-norepinephrine in all three brain regions. The GABAA agonist muscimol (100 microM) significantly augments 3H-norepinephrine release, but it is somewhat less effective than GABA. The GABAB agonist baclofen has little or no effect on basal 3H-norepinephrine efflux. GABA also augments both the magnitude and duration of electrically evoked 3H-norepinephrine release in slices from all three brain regions. GABA facilitation of electrically stimulated 3H-norepinephrine release is mediated through GABAA receptors as evidenced by its blockade by 10 microM bicuculline, a GABAA antagonist, but not by 200 microM 2-OH-saclofen, a GABAB antagonist. These data show that the inhibitory amino acid neurotransmitter GABA enhances both basal and evoked release of 3H-norepinephrine in brain slices from female rats. These effects are predominantly mediated by GABAA receptors. GABA modulation of hypothalamic norepinephrine release may play a role in the regulation of gonadotropin secretion and reproductive behaviors such as lordosis.
Asunto(s)
Corteza Cerebral/metabolismo , Hipotálamo/metabolismo , Norepinefrina/metabolismo , Área Preóptica/metabolismo , Ácido gamma-Aminobutírico/fisiología , Animales , Metabolismo Basal , Estimulación Eléctrica , Femenino , Técnicas In Vitro , Ratas , Ratas Sprague-Dawley , TritioRESUMEN
Exposure to the pheromones contained in female hamster vaginal secretions (FHVS) produces stereotypic, sex-specific behaviors in Syrian hamsters. Using Fos as a marker of neuronal stimulation we have found that (1) FHVS stimulates neurons in the posterior subdivision of the medial nucleus of the amygdala (MeP), the posterior medial subdivision of the bed nucleus of the stria terminalis (BNSTpm), and the magnocellular subdivision of the medial preoptic nucleus (MPN mag); (2) this stimulation is mediated by the main olfactory system; (3) stimulation of the MPN mag is regulated by testosterone in males; (4) stimulation of the BNSTpm and MeP is regulated by testosterone in females; and (5) FHVS does not induce Fos production in the MPN mag in females regardless of the hormonal state. These results support the hypothesis that the main olfactory system plays an important role in the regulation of pheromonally driven behaviors, identifies functional sex differences in pathways that regulate these behaviors, and emphasizes the different roles of the BNSTpm, MeP, and MPN mag in the regulation of male copulatory behavior.
Asunto(s)
Encéfalo/fisiología , Vías Olfatorias/fisiología , Feromonas , Testosterona/fisiología , Amígdala del Cerebelo/fisiología , Animales , Cricetinae , Femenino , Masculino , Mesocricetus , Modelos Biológicos , Especificidad de Órganos , Área Preóptica/fisiología , Proteínas Proto-Oncogénicas c-fos/biosíntesis , Caracteres Sexuales , Vagina/fisiologíaRESUMEN
The results of the present study indicate that (1) pheromones differentially stimulate neurons in males and females within a pathway that regulates copulatory behavior; and (2) testosterone (T) differentially regulates these sex differences. Exposure to the pheromones in FHVS (female hamster vaginal secretions) induces Fos immunoreactivity (Fos-IR) in the posterior subdivision of the medial nucleus of the amygdala (MeP) and the posteromedial subdivision of the bed nucleus of the stria terminalis (BNSTpm) of both sexes and stimulates the magnocellular subdivision of the medial preoptic nucleus (MPNmag) in males but not in females. Males also show more Fos in the MeP and BNSTpm than females. In the absence of T, gonadectomized males show greater FHVS-stimulated Fos-IR in the BNSTpm and MeP than gonadectomized females. T in females eliminates the sex difference in these regions. Only T-treated males show FHVS-stimulated Fos-IR within the MPNmag, and T has no effect on FHVS-stimulated Fos-IR within MPNmag in females. Thus, T influences FHVS-stimulated Fos-IR in the BNSTpm and MeP of females and the MPNmag of males. T also increases investigation (sniffing and licking) of FHVS in both males and females, but increases copulatory responses only in males. Our results indicate that T in the adult hamster differentially influences neural and behavioral responses to pheromone exposure in males and females. T only partially accounts for observed sex differences, and it is likely that neural organization during development also plays a role in influencing responses to pheromones.
Asunto(s)
Sistema Límbico/efectos de los fármacos , Feromonas/farmacología , Proteínas Proto-Oncogénicas c-fos/efectos de los fármacos , Testosterona/farmacología , Animales , Cricetinae , Femenino , Masculino , Caracteres SexualesRESUMEN
The medial nucleus of the amygdala (Me), bed nucleus of the stria terminalis (BNST), and medial preoptic area (MPOA) regulate copulation in the male hamster. The present study identified neuropeptide Y-immunoreactive (NPY-IR) neurons in the BNST and Me with the greatest concentration in the posteromedial and posteriordorsal subdivisions of these nuclei, respectively. NPY-IR filters are found in all three nuclei with dense plexi of NPY-IR varicosities in the most medial subdivisions. Substance P neurons are also densely concentrated in the posterior BNST and Me; however, no neurons contained both peptides. Thus, NPY and substance P neurons comprise two distinct populations within the BNST and Me of the hamster.
Asunto(s)
Sistema Límbico/química , Neuronas/química , Neuropéptido Y/aislamiento & purificación , Sustancia P/aislamiento & purificación , Amígdala del Cerebelo/química , Animales , Copulación/fisiología , Cricetinae , Inmunohistoquímica , Masculino , Mesocricetus , Área Preóptica/química , Núcleos Talámicos/química , Distribución TisularRESUMEN
Hamsters rely on chemosensory cues from females of the same species for the initiation of copulatory behavior. While these cues are detected by both the main and accessory olfactory systems it is the central nuclei in the accessory system that regulate mating behavior. The results of the present study indicate that exposure to vaginal secretions from a female Syrian hamster (FHVS) stimulates c-fos production in the medial nucleus of the amygdala (Me), the bed nucleus of the stria terminalis (BNST) and the medial preoptic area (MPOA). Exposure to vaginal secretions from Djungarian hamsters do not stimulate neurons in these areas. Thus the present results suggest that FHVS stimulates mating behavior by activating neurons within the vomeronasal pathway.
Asunto(s)
Sistema Límbico/metabolismo , Feromonas/farmacología , Proteínas Proto-Oncogénicas c-fos/biosíntesis , Conducta Sexual Animal/fisiología , Amígdala del Cerebelo/metabolismo , Animales , Cricetinae , Femenino , Inmunohistoquímica , Sistema Límbico/efectos de los fármacos , Sistema Límbico/fisiología , Masculino , Mesocricetus , Vías Olfatorias/efectos de los fármacos , Vías Olfatorias/fisiología , Phodopus , Área Preóptica/metabolismo , Proteínas Proto-Oncogénicas c-fos/inmunología , Especificidad de la Especie , Tálamo/metabolismo , Vagina/metabolismo , Vagina/fisiologíaRESUMEN
GABAergic neurotransmission has been implicated in the control of the steroid-dependent behavior, lordosis. GABA has dual effects on lordosis: it facilitates lordosis through actions in the medial hypothalamus (mHYP) and it inhibits lordosis through actions in the preoptic area (POA). In the present study, gonadally intact and ovariectomized female rats were behaviorally tested with a sexually active male. Brains were removed from sexually receptive female either 1 or 24 h after behavioral testing. There was a significant difference in endogenous GABA concentration in HYP and POA between receptive, postreceptive and ovariectomized nonreceptive females. Specifically, GABA levels in postreceptive females were higher in the HYP (20%) and lower in the POA (21%) in comparison to receptive females (p less than 0.05). There was also a significant change in binding parameters of 3H-muscimol in the HYP and POA of receptive females as compared to 24 h postreceptive and ovariectomized rats. Attempts to modulate 3H-GABA release from hypothalamic tissue slices by estrogen or progesterone in ovariectomized rats yielded no effect on this parameter.