Perinatal Docosahexaenoic Acid Supplementation Improves Cognition and Alters Brain Functional Organization in Piglets.

Epidemiologic studies associate maternal docosahexaenoic acid (DHA)/DHA-containing seafood intake with enhanced cognitive development; although, it should be noted that interventional trials show inconsistent findings. We examined perinatal DHA supplementation on cognitive performance, brain anatomical and functional organization, and the brain monoamine neurotransmitter status of offspring using a piglet model. Sows were fed a control (CON) or a diet containing DHA (DHA) from late gestation throughout lactation. Piglets underwent an open field test (OFT), an object recognition test (ORT), and magnetic resonance imaging (MRI) to acquire anatomical, diffusion tensor imaging (DTI), and resting-state functional MRI (rs-fMRI) at weaning. Piglets from DHA-fed sows spent 95% more time sniffing the walls than CON in OFT and exhibited an elevated interest in the novel object in ORT, while CON piglets demonstrated no preference. Maternal DHA supplementation increased fiber length and tended to increase fractional anisotropy in the hippocampus of offspring than CON. DHA piglets exhibited increased functional connectivity in the cerebellar, visual, and default mode network and decreased activity in executive control and sensorimotor network compared to CON. The brain monoamine neurotransmitter levels did not differ in healthy offspring. Perinatal DHA supplementation may increase exploratory behaviors, improve recognition memory, enhance fiber tract integrity, and alter brain functional organization in offspring at weaning.

Reduced home cage and social activity in Pou3f2⊿ mice.

Pou3f2/Brn2 is a transcription factor that helps to determine the cellular identity of neocortical or hypothalamic neurons. Mammalian Pou3f2 contains three homopolymeric amino acids that are not present in amphibian Pou3f2. These amino acids contribute to monoamine function, which may play specific roles in mammalian development and behavior. Previous work has indicated that Pou3f2⊿ mice, which lack the homopolymeric amino acids, exhibited declined maternal activity and impaired object and spatial recognition. The current study, analyzed weight gain, brain development, home cage activity, social interaction, and response to novel objects in Pou3f2⊿ mice to determine which aspects of behavior were affected by monoamine dysregulation. Compared to their wild type counterparts, Pou3f2⊿ mice showed decreased social interaction and reduced home cage activity during their active phase. However, they showed normal weight gain, brain development, and responses to novelty. These results indicate that monoamine dysregulation in Pou3f2⊿ mice may specifically affect basal activity and social development, without altering non-social motivation.

Evidence for the Involvement of Monoaminergic Pathways in the Antidepressant-Like Activity of Cymbopogon citratus in Mice.

Objectives Depression is a complex neuropsychiatric disorder, which affects the quality of life of the sufferers and treatment approach is associated with serious adverse effects and sometimes therapeutic failures. Cymbopogon citratus leaf (CC) has been reported to exert anti-depressant effect but its mechanism of action is yet to be elucidated hence, the need for this study. Methods The anti-depressant-like effect of Cymbopogon citratus aqueous leaf was evaluated using forced swim test (FST), tail suspension test (TST) and yohimbine-induced lethality test (YLT) in aggregated mice. Interaction studies involving p-chlorophenylalanine (pCPA), an inhibitor of serotonin biosynthesis and yohimbine, α2-adrenergic receptor antagonist were carried out to evaluate the role of monoaminergic system in the anti-depressant-like effect of CC. The effect of CC on spontaneous motor activity (SMA) was also assessed using activity cage. ResultsCymbopogon citratus (25 and 50 mg/kg, p.o.) demonstrated antidepressant-like activity devoid of significant stimulation of the SMA in mice. However, the antidepressant-like property of CC was significantly (p<0.05) attenuated by pretreatment with yohimbine suggesting involvement of noradrenergic pathway in the action of the extract. Also, pCPA reversed the anti-immobility effect of CC, indicating the role of serotonergic system in the mediation of its antidepressant activity. Moreover, CC (25 and 50 mg/kg) potentiated the lethal effect of yohimbine in aggregated mice, which further suggest the involvement of monoaminergic systems in its action. Conclusions The results of the study showed that C. citratus might be interacting with serotonergic and noradrenergic pathways to mediate its anti-depressant-like effect in mice.

Antidepressant-like effect of the hydroethanolic leaf extract of Alchornea cordifolia (Schumach. & Thonn.) Mull. Arg. (Euphorbiaceae) in mice: involvement of monoaminergic system.

ETHNOPHARMACOLOGICAL RELEVANCE: The leaf of Alchornea cordifolia (Euphorbiaceae) is used in traditional African medicine in the treatment of various neurological and psychiatric disorders including depression. Previous studies have shown its potent antidepressant-like effect in the forced swimming test (FST). Hence, this study sought to investigate the involvement of monoaminergic systems in the antidepressant-like effect elicited by hydroethanolic leaf extract of Alchornea cordifolia (HeAC) in the FST. MATERIALS AND METHODS: HeAC (25-400mg/kg, p.o.) was administered 1h before the FST. To investigate the contribution of monoaminergic systems to antidepressant-like effect, receptors antagonists were injected 15min before oral administration of HeAC (200mg/kg) to mice and 1h thereafter, subjected to FST. RESULTS: HeAC (200 and 400mg/kg, p.o.) produced dose dependent and significant (P<0.001) antidepressant-like effect, in the FST, without accompanying changes in spontaneous locomotor activities in the open-field test. The anti-immobility effect of HeAC (200mg/kg) in the FST was prevented by pretreatment of mice with SCH 23390 (0.05mg/kg, s.c., a dopamine D1 receptor antagonist), sulpiride (50mg/kg, i.p., a dopamine D2 receptor antagonist), prazosin (1mg/kg, i.p., an α1-adrenoceptor antagonist), yohimbine (1mg/kg, i.p., an α2-adrenoceptor antagonist), and GR 127993 (5-HT1B receptor antagonist). Similarly, 3 days intraperitoneal injection of p-chlorophenylalanine (pCPA, 150mg/kg, i.p., an inhibitor of serotonin synthesis) prevented the antidepressant-like effect elicited by HeAC. The combination of subeffective doses of imipramine (5mg/kg, p.o.) or fluoxetine (5mg/kg, p.o.), with HeAC (25mg/kg, p.o., subeffective dose) produced a synergistic antidepressant-like effect in the FST. CONCLUSION: The hydroethanolic extract of Alchornea cordifolia possesses antidepressant-like effect mediated through interaction with dopamine (D1 and D2), noradrenergic (α1 and α2 adrenoceptors), and serotonergic (5HT1B receptors) systems. Also, the potentiation of the anti-immobility effect of conventional antidepressants (fluoxetine and imipramine) by Alchornea cordifolia suggest potential therapeutic effect in depression.

[Neurobiology of attention deficit hyperactivity disorder]. / Neurobiologische Grundlagen der Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung.

The origin of ADHD is multifactorial and both the aetiology and pathophysiology of ADHD are as yet incompletely understood. The monoamine deficit hypothesis of ADHD postulates a dysbalance in the interaction of the neurotransmitters dopamine, noradrenaline and serotonin. Pathophysiological mechanisms involved in ADHD include alterations in fronto-striatal circuits. The currently proposed animal models of ADHD are heterogeneous with regard to their pathophysiological alterations and their ability to mimic behavioural symptoms and to predict response to medication. Some evidence points to a genetic basis for ADHD which is likely to involve many genes of small individual effects. In summary, specific neurobiological substrates of ADHD are unknown and multiple genetic and environmental factors appear to act together to create a spectrum of neurobiological liability.

Social-cooperation differs from individual behavior in hypothalamic and striatal monoamine function: evidence from a laboratory rat model.

Explanations and models of cooperation usually focus on the economics of an individual's invested effort and outcomes while down-playing social dimensions of naturally occurring cooperation. This study examined whether cooperative and individual behaviors differ in monoaminergic function in a manner that may explain the reported 'bias for cooperation' even under conditions where no immediate economic gains exist. Cooperation, represented by pairs of rats reinforced for coordinated shuttles within a shared chamber (COOP), was compared with rats shuttling for reinforcements individually (IND), and behaviorally naïve rats (NAïVE). Following training, the hypothalamus and striata were sampled and the activity patterns of the noradrenergic, serotonergic and dopaminergic systems were assessed using HPLC analyses. By matching the proportions of reinforced individual shuttles for COOP and IND rats the economic differences of invested effort (shuttles) and outcomes (obtained reinforcements) were neutralized. Nevertheless, differences were evident in monoaminergic functions. In comparison with IND rats, COOP rats showed significantly higher hypothalamic norepinephrine levels and exhibited a trend toward higher striatal serotonin levels. Differences in levels of dopaminergic metabolites were restricted to the right striatum; compared to IND rats, COOP rats exhibited significantly higher levels of HVA, whereas NAÏVE rats exhibited significantly higher DOPAC levels. Since economic differences between cooperative and individual shuttling were neutralized, the results demonstrate a relationship between social cooperation and a distinct activity pattern in brain mechanisms that were related with arousal, goal directed behaviors and motivation and further highlight the key role of social behaviors in the reported 'bias for cooperation'.

Monoamine reuptake inhibition and mood-enhancing potential of a specified oregano extract.

A healthy, balanced diet is essential for both physical and mental well-being. Such a diet must include an adequate intake of micronutrients, essential fatty acids, amino acids and antioxidants. The monoamine neurotransmitters, serotonin, dopamine and noradrenaline, are derived from dietary amino acids and are involved in the modulation of mood, anxiety, cognition, sleep regulation and appetite. The capacity of nutritional interventions to elevate brain monoamine concentrations and, as a consequence, with the potential for mood enhancement, has not been extensively evaluated. The present study investigated an extract from oregano leaves, with a specified range of active constituents, identified via an unbiased, high-throughput screening programme. The oregano extract was demonstrated to inhibit the reuptake and degradation of the monoamine neurotransmitters in a dose-dependent manner, and microdialysis experiments in rats revealed an elevation of extracellular serotonin levels in the brain. Furthermore, following administration of oregano extract, behavioural responses were observed in mice that parallel the beneficial effects exhibited by monoamine-enhancing compounds when used in human subjects. In conclusion, these data show that an extract prepared from leaves of oregano, a major constituent of the Mediterranean diet, is brain-active, with moderate triple reuptake inhibitory activity, and exhibits positive behavioural effects in animal models. We postulate that such an extract may be effective in enhancing mental well-being in humans.

Involvement of monoamines and proinflammatory cytokines in mediating the anti-stress effects of Panax quinquefolium.

Panax quinquefolium (PQ) is well acclaimed in literature for its effects on central and peripheral nervous system. The present study explores the effects of PQ on stress induced changes of corticosterone level in plasma, monoamines (NA, DA and 5-HT) and interleukin (IL-2 and IL-6) levels in cortex and hippocampus regions of brain and also indicate their possible roles in modulating stress. Mice subjected to chronic unpredictable stress (CUS, for 7 days) showed significant increase in plasma corticosterone level and depletion of noradrenaline (NA), dopamine (DA) and 5-hydroxytryptamine (5-HT) levels in cortex and hippocampal regions along with an increased level of IL-2 and IL-6 in the same areas. Aqueous suspension of PQ was administered daily at a dose of 100 and 200mg/kg p.o. prior to the stress regimen and its effects on selected stress markers in plasma and brain was evaluated. PQ at a dose of 200mg/kg p.o. was found to be effective in normalizing the CUS induced elevation of plasma corticosterone and IL-2, IL-6 levels in brain. Moreover, it was significantly effective in reinstating the CUS induced depletion of NA, DA and 5-HT in hippocampus, while NA and 5-HT in cortex of brain. However, PQ at a dose of 100mg/kg p.o. was found ineffective in regulating any of these CUS induced changes. Present study provides an insight into the possible role of PQ on hyperactive HPA axis in the regulation of immediate stress effectors like corticosterone, cytokines and brain monoamines. In this study, PQ has emerged as a potential therapeutic in the cure of stress related disorders and needs to be evaluated in clinical studies to ascertain its efficacy.

Dopaminergic function in depressed patients with affective flattening or with impulsivity: [18F]fluoro-L-dopa positron emission tomography study with voxel-based analysis.

A decreased striatal presynaptic dopaminergic function has been reported in depressed patients with affective flattening and psychomotor retardation, using (18)F-fluorodopa positron emission tomography and regions-of-interest. The present study aimed to investigate regional ;[(18)F]dopa uptake in mesolimbic and mesocortical dopaminergic projections with the hypothesis that there should be a decrease in mesolimbic [(18)F]dopa uptake associated with affective flattening and psychomotor retardation. [(18)F]Dopa-positron emission tomography and anatomical magnetic resonance imaging datasets from 12 screened depressed patients with either marked affective flattening and psychomotor retardation (n=6) or with marked impulsivity (n=6), and from eight healthy subjects, were analyzed using a voxel-based approach. Regional differences in [(18)F]dopa uptake rate constant (K(i)) values between the healthy group and the two depression subgroups were compared using both statistical parametric mapping and cluster-based regions-of-interest. Patients with affective flattening and psychomotor retardation had [(18)F]dopa K(i) decreases in the left caudate, bilateral putamen and nucleus accumbens, left parahippocampus and dorsal brainstem. Impulsive depressives had [(18)F]dopa K(i) decreases in the anterior cingulate and hypothalamus, and an increase in the right parahippocampal gyrus. These findings support distinct regional dysfunctions of monoamines depending on the depressive symptomatology.

Omega-3 fatty acids and monoamine neurotransmission.

We proposed several years ago that the behavioral effects of n-3 PUFA deficiency observed in animal models might be mediated through the dopaminergic and serotonergic systems that are very involved in the modulation of attention, motivation and emotion. We evaluated this hypothesis in an extended series of experiments on rats chronically diet-deficient in alpha-linolenic acid, the precursor of long-chain n-3 PUFA, in which we studied several parameters of these neurotransmission systems. The present paper synthesizes the main data we obtained on interactions between n-3 PUFA status and neurotransmission in animal models. We demonstrated that several parameters of neurotransmission were affected, such as the vesicular pool of dopamine and serotonin, thus inducing several regulatory processes such as modification of cerebral receptors in specific brain areas. We also demonstrated that (i) a reversal diet with adequate n-6 and n-3 PUFA given during the lactating period to rats originating from alpha-linolenic acid-deficient dams was able to restore both the fatty acid composition of brain membranes and several parameters of the dopaminergic and serotonergic neurotransmission, and (ii) when given from weaning, this reversal diet allowed partial recovery of biochemical parameters, but no recovery of neurochemical factors. The occurrence of profound n-3 PUFA deficiency during the lactating period could therefore be an environmental insult leading to irreversible damage to specific brain functions. Strong evidence is now showing that a profound n-3 PUFA experimental deficiency is able to alter several neurotransmission systems, at least the dopaminergic and serotonergic. Whether these experimental findings can be transposed to human pathophysiology must be taken cautiously, but reinforces the hypothesis that strong links exist between the PUFA status, aspects of brain function such as neurotransmission processes and behavior.

Cybernetic principles in the systematic concept of hypothalamic feeding control.

Research on biological mechanisms of eating behavior and related disorders, such as obesity and anorexia nervosa, has become a large field of research in the last 15 years. With the discovery of peptides related to hypothalamic control of food intake (e.g. leptin and ghrelin) the search for the biological 'master key' of feeding control was renewed. As a result, mid-20th century biological concepts based on systematic and cybernetic thoughts fell into oblivion. This review highlights discoveries of hypothalamic-controlled feeding and eating behavior with a cybernetic and systematic perspective. Interestingly, older ideas of hypothalamic function offer possibilities for the incorporation of new molecular discoveries into systematic concepts of feeding behavior.

The organization of the brainstem and spinal cord of the mouse: relationships between monoaminergic, cholinergic, and spinal projection systems.

Information regarding the organization of the CNS in terms of neurotransmitter systems and spinal connections in the mouse is sparse, especially at the level of the brainstem. An overview is presented of monoaminergic and cholinergic systems in the brainstem and spinal cord that were visualized immunohistochemically in inbred C57BL/6 and outbred CD-1 mice. This information is complemented with data on spinal cord-projecting systems that were characterized using retrograde tracing, spinal hemisections, and double labeling techniques. Attention is given to differences in these systems related to spinal levels. The data are discussed with reference to studies in the rat, and to standardized information as provided in the atlas of the mouse brain. Although the overall organization of these systems in the mouse is largely similar to those in the rat, species differences are present in relative location, size and/or connectivity of cell groups. For example, catecholaminergic neurons in the (ventro)lateral pons (A5 and A7 cell groups) in the mouse project to the spinal cord mainly via contralateral, and not ipsilateral, pathways. The data further supplement information as provided in standardized brainstem sections of the C57BL/6 mouse [Paxinos, G., Franklin, K.B.J., 2001. The mouse brain in stereotaxic coordinates. Academic Press, San Diego], especially with respect to the size and/or location of the catecholaminergic retrorubral field (A8 group), A5, A1, and C1 cell groups, and the serotonergic B4 group, reticulotegmental nucleus (B9 group), lateral paragigantocellular nucleus and raphe magnus nucleus (B3 group). Altogether this study provides a comprehensive overview of the spatial relationships of neurochemically and anatomically defined neuronal systems in the mouse brainstem and spinal cord.

Neural monoaminergic mediation of the effect of St. John's wort extract on prepulse inhibition of the acoustic startle response in rats.

Prepulse inhibition (PPI) of startle response is a valuable paradigm for sensorimotor gating processes by which an organism filters sensory information. Disruption of PPI is evident in schizophrenia and Huntington's disease among other neuropsychiatric disorders characterized by sensorimotor gating deficit. In such disorders, increased brain monoamines' transmission was suggested to underlie PPI disruption. The effect of St. John's wort extract on PPI of startle response is yet to be investigated despite research findings indicating augmented levels of brain monoaminergic function after acute administration of the extract. In this study, the effect of acute oral administration of St. John's wort extract (62.5, 125, 250 and 500 mg/kg) was tested on PPI of an acoustic startle response in rats. A disruption of PPI resulted after the administration of the highest dose of the extract and therefore its effect on dopaminergic, serotonergic and noradrenergic neurotransmission was investigated in a number of rat brain areas involved in mediation of PPI response. Results demonstrated that 500 mg/kg of the extract augmented dopaminergic transmission in the thalamus together with elevating noradrenergic transmission in both brainstem and hippocampus. In addition, increased serotonin levels in brainstem, thalamus, cortex and hippocampus were evident after administration of the same dose of the extract. It was therefore concluded that St. John's wort extract (500 mg/kg) reduced PPI response possibly through enhancing monoaminergic transmission in brainstem, thalamus, cortex and/or hippocampus. Clinical investigations are therefore needed to determine whether St. John's wort extract may affect sensorimotor gating in both schizophrenia and Huntington's disease.

Chronic social stress: effects on limbic brain structures.

Different types of stressors are known to activate distinct neuronal circuits in the brain. Acute physiological stimuli that are life threatening and require immediate reactions lead to a rapid stimulation of brainstem and hypothalamus to activate efferent visceral pathways. In contrast, psychological stressors activate higher-order brain structures for further interpretations of the perceived endangerment. Common to the later multimodal stressors is that they need cortical processing and, depending on previous experience or ongoing activation, the information is assembled within limbic circuits connecting, e.g., the hippocampus, amygdala and prefrontal cortex to induce neuroendocrine and behavioral responses. In view of the fact that stressful life events often contribute to the etiology of psychopathologies such as depressive episodes, several animal models have been developed to study central nervous mechanisms that are induced by stress. The present review summarizes observations made in the tree shrew chronic psychosocial stress paradigm with particular focus on neurotransmitter systems and structural changes in limbic brain regions.

Influence of time of day on hypothalamic monoaminergic activity in early pregnancy: effect of a previous reproductive experience.

Several dopamine-related neurochemical and behavioral responses are influenced by the time of day. The light-dark shift is a major zeitgeber for various functionally important hypothalamic monoaminergic systems. However, these influences are modulated by reproductive state and by reproductive experience (RE) in females. Early pregnancy in rodents generates diurnal and nocturnal prolactin surges that are reduced in intensity in a second pregnancy. Dopamine (DA) is a major inhibitory factor of prolactin synthesis and secretion. Other neurotransmitters such as serotonin (5HT) and norepinephrine (NE) can modulate prolactin secretion as well. Previous works have demonstrated that RE induces changes in central concentrations of both dopamine and serotonin. In addition, RE modulates the responses of both dopaminergic and serotoninergic nerve terminals. The present investigation was designed to examine the possible effects of RE on hypothalamic concentrations of DA, NE, 5HT and their major metabolites homovanillic acid (HVA), 3-4-dihydroxyphenyl acetic acid (DOPAC), 3-methoxy mandelic acid (VMA) and 5-hydroxyindole 3-acetic acid (5HIAA), respectively. These parameters were measured in pregnant rats during the light-dark shift and the prolactin surges. Primi- and multigravid rats were sacrificed on the 7th-8th day of pregnancy between 1700 and 1900 h (light-dark shift and diurnal prolactin surge) or 0200 and 0400 h (nocturnal prolactin surge), and hypothalamic concentrations of DA, NE and 5HT and their metabolites were measured by high performance liquid chromatography coupled to an electrochemical detector (HPLC-ED). Trunk blood was collected and serum prolactin measured by radioimmunoassay. The prolactin surge was confirmed and multigravid rats showed significantly lower serum prolactin levels as compared to primigravid rats between 0200 and 0400 h. During the light-dark shift DA and NE concentrations increased while DOPAC/DA, HVA/DA and 5HIAA/5HT ratios decreased in multigravid rats compared to primigravid rats. Except for 5HIAA/5HT, these differences were not observed during the prolactin nocturnal surge. These results suggest that a previous reproductive experience induces central functional changes during pregnancy which are expressed differently according to the time of day.

Maternal obesity alters adiposity and monoamine function in genetically predisposed offspring.

The impact of maternal obesity on brain monoamine function in adult offspring of dams selectively bred to express diet-induced obesity (DIO) or diet resistance (DR) was assessed by making dams obese or lean during gestation and lactation. After 12 wk on chow and 4 wk on a 31% fat diet, offspring hypothalamic nucleus size and [(3)H]nisoxetine binding to norepinephrine transporters (NET) and [(3)H]paroxetine binding to serotonin transporters (SET) were measured. Offspring of obese DIO dams became more obese than all other groups, but maternal obesity did not alter weight gain in DR offspring (25). Maternal obesity was associated with 10-17% enlargement of ventromedial nuclei (VMN) and dorsomedial nuclei in both DIO and DR offspring. Offspring of obese DIO dams had 25-88% lower NET binding in the paraventricular nuclei (PVN), arcuate nuclei, VMN, and the central amygdalar nuclei, while offspring of obese DR dams had 43-67% higher PVN and 90% lower VMN NET binding and a generalized increase in SET binding across all hypothalamic areas compared with other groups. Thus maternal obesity was associated with alterations in offspring brain monoamine metabolism, which varied as a function of genotype and the development of offspring obesity.

Amine modulation of the transient potassium current in identified cells of the lobster stomatogastric ganglion.

The pyloric network of the stomatogastric ganglion of the lobster Panulirus interruptus is a model system used to understand how motor networks change their output to produce a variety of behaviors. The transient potassium current (I(A)) shapes the activity of individual pyloric neurons by affecting their rate of postinhibitory rebound and spike frequency. We used two electrode voltage clamp to study the modulatory effects of dopamine (DA), octopamine (OCT), and serotonin (5-HT) on I(A) in the anterior burster (AB), inferior cardiac (IC), and ventricular dilator (VD) neurons of the pyloric circuit. DA significantly reduced I(A) in the AB and IC neurons and shifted their voltages of activation (V(act)) and inactivation (V(inact)) in a depolarized direction. These ionic changes contribute to the depolarization and increased firing rate of the AB and IC neurons produced by DA. Likewise, 5-HT significantly reduced I(A) and shifted V(inact) in the depolarized direction in the IC neuron, consistent with 5-HT's enhancement of IC firing. None of the amines evoked significant changes in I(A) in the VD neuron, suggesting that other currents mediate the amine effects on this neuron.

Hypothalamo-pituitary-gonadal axis in control of female reproductive cycle.

Gonadotropin-releasing hormone (GnRH) secretion from the hypothalamus is pivotal to the regulation of reproductive physiology in vertebrates. The characteristic periodic secretion of gonadotropin releasing hormone (GnRH) from the medial basal hypothalamus (MBH), at the rate of one pulse an hour is essential for the maintenance of the menstrual cycle. These pulses are due to oscillations in the electrical activity of the GnRH pulse generator in the MBH. The GnRH pulse generator is under the influence of an assortment of interactions of multiple neural, hormonal and environmental inputs to the hypothalamus. Hence, a number of conditions such as stress, drug intake, exercise, sleep affect the activity of this pulse generator. Any deviation of normal frequency results in disruption of normal cycle. The cycle can become anovulatory in the hypothalamic lesions and can be restored by exogenous administration of pulsatile GnRH. Of late, studies have shown that pulse generator activity is also maintained by specific metabolic signals meant for energy homeostasis. Studies are in progress to work out cellular basis of GnRH pulse generator's rhythmic activation and role of Ca++ as second messenger for GnRH stimulated gonadotropin release. New concepts are emerging to find the existence of an FSH releasing factor, which independently regulates the activity of FSH.

Monoaminergic activities of limbic regions are elevated during aggression: influence of sympathetic social signaling.

A visual social signal inhibiting aggression is coincident with limiting serotonergic and noradrenergic activity in subiculum, hippocampus, nucleus accumbens, medial amygdala, but not lateral amygdala, septum, and hypothalamus. Darkening of postorbital skin in the lizard Anolis carolinensis is stimulated by sympathetic activation of beta(2)-adrenergic receptors via adrenal catecholamines, and occurs more rapidly in dominant males during social interaction. Eyespot darkening functions as a social signal limiting aggressive interaction. To assess the effect of this social signal on telencephalic activity of monoamines, males were painted postorbitally with green or black paint, and exposed to a mirror. Serotonergic and noradrenergic turnover, as estimated by ratios of catabolite to transmitter, were elevated in the subiculum, hippocampus, nucleus accumbens, and medial amygdala of animals in which the eyespots were masked by green paint. Conversely, dopaminergic activity in these brain regions was lower in males with hidden eyespots (painted green). Hiding the eyespot evoked significantly increased aggressive activity toward the mirror image. Furthermore, changes in monoaminergic turnover were coincident with altered aggressive behavior, suggesting a relationship between them. Changes of monoaminergic activity were not observed in the septum, lateral amygdala, or hypothalamus, when males with eyespots permanently marked (black) were compared with those with eyespots hidden (painted green). Stimulated (serotonergic and noradrenergic) or inhibited (dopaminergic) activity due to social signal and aggression are confined to regions of the brain similarly activated during social stress, and do not constitute a generalized activation of monoaminergic systems.