Alpha1 receptor antagonist in the median raphe nucleus evoked hyperphagia in free-feeding rats.

Serotonergic neurons in the median raphe nucleus (MnR) are stimulated by α(1)-adrenergic agonists and inhibited by α(2)-agonists. This study investigated the effect of the blockade of the MnR α(1)-adrenergic receptors of free feeding rats as an attempt to elucidate the functional role of these receptors in the control of feeding behavior. In addition, an α(2)-receptor antagonist was also administered in the MnR in order to strengthen the previous suggestion that α(2)-adrenergic receptors participate in the control of feeding behavior, probably decreasing the facilitatory influence on MnR serotonergic neurons. The α(1)-adrenergic antagonist prazosin (PRA, 40 nmol) or vehicle was injected into the MnR 15 min before treatment with phenylephrine (PHE, 0.2 nmol). The α(2)-adrenergic antagonist yohimbine (YOH, 40 nmol) was administered 15 min before clonidine (CLO, 20 nmol) or vehicle in free-feeding rats. After the injections, the animals were placed in the feeding chamber for 30 min to evaluate the ingestive and non-ingestive behaviors. At the end of the experiment the quantity of food and water consumed were measured. While treatment with PRA in the MnR followed by PHE did not change the feeding behavior, PRA injection alone into the MnR caused hyperphagia accompanied by a reduction in the latency to start eating, an increase in feeding frequency and an increase in the feeding duration. Pretreatment with YOH in the MnR blocked the hyperphagic effect induced by CLO. The present data reinforce our previous suggestion that the MnR α(2)-adrenergic receptors participate in the control of feeding behavior, probably decreasing the facilitatory influence on MnR serotonergic neurons of free-feeding animals. Furthermore, these results indicate that this influence is tonically mediated by α(1)-adrenergic receptors upon MnR neurons, which inhibit food intake.

Telencephalic distributions of doublecortin and glial fibrillary acidic protein suggest novel migratory pathways in adult lizards.

Adult neurogenesis has been reported in all major vertebrate taxa. However, neurogenic rates and the number of neurogenic foci vary greatly, and are higher in ancestral taxa. Our study aimed to evaluate the distribution of doublecortin (DCX) and glial fibrillary acidic protein (GFAP) in telencephalic areas of the adult tropical lizard Tropidurus hispidus. We describe evidence for four main neurogenic foci, which coincide anatomically with the ventricular sulci described by the literature. Based on neuronal morphology, we infer four migratory patterns/pathways. In the cortex, patterns of GFAP and DCX staining support radial migrations from ventricular zones into cortical areas and dorsoventricular ridge. Cells radiating from the sulcus septomedialis (SM) seemed to migrate to the medial cortex and dorsal cortex. From the sulcus lateralis (SL), they seemed to be bound for the lateral cortex, central amygdala and nucleus sphericus. We describe a DCX-positive stream originating in the caudal sulcus ventralis and seemingly bound for the olfactory bulb, resembling a rostral migratory stream. We provide evidence for a previously undescribed tangential dorso-septo-caudal migratory stream, with neuroblasts supported by DCX-positive fibers. Finally, we provide evidence for a commissural migration stream seemingly bound for the contralateral nucleus sphericus. Therefore, in addition to two previously known migratory streams, this study provides anatomical evidence in support for two novel migratory routes in amniotes.

Proanthocyanidin-rich fraction from Croton celtidifolius Baill confers neuroprotection in the intranasal 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine rat model of Parkinson's disease.

We have recently demonstrated that rodents treated intranasally with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) suffered impairments in olfactory, cognitive and motor functions associated with time-dependent disruption of dopaminergic neurotransmission in different brain structures conceivably analogous to those observed during different stages of Parkinson's disease (PD). On the other hand, the proanthocyanidin-rich fraction (PRF) obtained from the bark of Croton celtidifolius Baill (Euphorbiaceae), a tree frequently found in the Atlantic forest in south Brazil, has been described to have several neurobiological activities including antioxidant and anti-inflammatory properties, which may be of interest in the treatment of PD. The present data indicated that the pretreatment with PRF (10 mg/kg, i.p.) during five consecutive days was able to prevent mitochondrial complex-I inhibition in the striatum and olfactory bulb, as well as a decrease of the enzyme tyrosine hydroxylase expression in the olfactory bulb and substantia nigra of rats infused with a single intranasal administration of MPTP (1 mg/nostril). Moreover, pretreatment with PRF was found to attenuate the short-term social memory deficits, depressive-like behavior and reduction of locomotor activity observed at different periods after intranasal MPTP administration in rats. Altogether, the present findings provide strong evidence that PRF from C. celtidifolius may represent a promising therapeutic tool in PD, thus being able to prevent both motor and non-motor early symptoms of PD, together with its neuroprotective potential.

Expression of aggressiveness modulates mesencephalic c-fos activation during a social interaction test in Japanese quail (Coturnix japonica).

It is well known that during a social conflict, interactions are dependent on the animal's propensity to behave aggressively as well as the behavior of the opponent. However, discriminating between these two confounding factors was difficult. Recently, a Social Interaction (SI) test using photocastrated males as non-aggressive stimuli was proposed as a useful tool to evaluate aggressiveness. The avian Intercollicular- Griseum centralis complex (comparable to mammalian periaqueductal gray) has been reported as a crucial node in the descending pathways that organize behavioral and autonomic aspects of defensive responses and aggressiveness. Herein, using the SI test, we evaluated whether mesencephalic areas are activated (expressed c-fos) when photostimulated adult males are confronted with non-responsive (non-aggressive) opponents. Furthermore, we also examined whether mesencephalic activation is related to male performance during the SI test (i.e., aggressive vs. non-aggressive males) in birds reared in enriched or in standard environments. Five mesencephalic areas at two anatomic levels (intermediate and rostral) and locomotion during SI testing were studied. Aggressive males showed increased c-fos expression in all areas studied, and moved at faster speeds in comparison to their non-aggressive and control counterparts. Non-aggressive males and the test controls showed similar c-fos labeling. In general, rearing condition did not appear to influence c-fos expression nor behavior during the SI test. Findings suggest that mesencephalic activation is involved when males are actively expressing aggressive behaviors. This overall phenomenon is shown regardless of both the environmental stimuli provided during the birds´ rearing and the potentially stressful stimuli during the SI trial.

Behavioral and metabolic effects of central injections of orexins/hypocretins in pigeons (Columba livia).

In the present study, the acute behavioral and ingestive effects of ICV injections of mammalian orexin-A (ORXA; vehicle, 0.2, 0.6 or 2 nmol) and of orexin-B (ORXB; vehicle, 0.2, 0.6 or 2 nmol), as well as possible long-term effects (through 24 h of continuous intake monitoring after 0.6 nmol of ORXA or ORXB) of these treatments in food/water intake and in blood levels of metabolic fuels (free fatty acids and glucose, after 0.2 or 0.6 nmol of ORXA) were examined in adult male pigeons. Both ORXA and ORXB treatments failed to produce acute (1-3 h) or long-term effects on feeding and drinking behaviors, and did not change blood free fatty acids and glucose 15 and 30 min after treatments, as compared to vehicle-treated animals. However, ORXA (but not ORXB) treatments evoked a dose-related, intense increase in exploratory behaviors, associated to reduced time spent in alert immobility and sleep-typical postures. These data substantiate the lack of orexigenic effects of ORXs in avian species, and suggest that an important role in vigilance control may represent a conserved functional attribute of orexinergic circuits in vertebrates.

The microinjection of AMPA receptor antagonist into the accumbens shell, but not into the accumbens core, induces anxiolysis in an animal model of anxiety.

This study investigated the effect of the AMPA receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX) microinjected into the core and shell sub-regions of the accumbens nucleus (Acb), on the level of fear/anxiety and emotional learning, in female rats submitted to the elevated plus-maze (EPM), an animal model of anxiety. Bilateral microinjections of DNQX (330 and 660 ng) into the Acb shell (AP, +1.08 to +2.16) induced an anxiolytic-like effect in relation to rats microinjected with vehicle, since there was an increased percentage of entries in the open arms of the maze. The 660 ng DNQX microinjection into the Acb shell also increased the percentage of entries into the open arms in relation to 660 ng DNQX microinjection into the Acb core. Prior DNQX microinjections in both core and shell sub-regions of the Acb failed to impair the emotional learning, since the animals exhibited an increase of the open arm avoidance on EPM Trial 2 in relation to EPM trial 1. DNQX microinjections into both sub-regions of the Acb did not change the number of entries into the enclosed arms, either in the EPM Trial 1 or in the EPM Trial 2, which indicates an absence of drug-induced locomotor impairment. Similarly, DNQX microinjections into both sub-regions of the Acb failed to alter the total arm entries, rearing, grooming and head-dipping frequency. The anxiolytic-like effect induced by DNQX suggests that the AMPA receptor in the Acb shell, but not in the Acb core, may underlie anxiety regulation in the EPM.

The effects of metergoline and 8-OH-DPAT injections into arcuate nucleus and lateral hypothalamic area on feeding in female rats during the estrous cycle.

The present study examined the effects of local injections of metergoline (MET, an antagonist of 5-HT1/2 receptors, 2 and 20 nmol) and 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT, selective 5-HT1A receptor agonist, 0.6 and 6 nmol) into the arcuate nucleus (ARC) and the lateral hypothalamus (LH), on ingestive and non-ingestive behaviors of female rats. These effects were examined during the diurnal periods of diestrus and estrus in rats adapted to eat a wet mash diet (enriched with 10% sucrose) during 1h for 3 consecutive days at the recording chamber. The results showed that 8-OH-DPAT injected into the LH significantly reduced food intake at all doses and both cycle stages, while in the ARC these treatments evoked hypophagia only at the highest 8-OH-DPAT dose and only at the estrous phase. MET administered into the ARC (at all doses) failed to affect food intake during both estrous stages. On the other hand, food intake decreased after injection of both doses of MET into the LH of rats during estrous and diestrus phases. In estrus stage, injections of the higher dose of 8-OH-DPAT into the ARC and into the LH decreased the duration of feeding. Latency to start feeding, drinking, and non-ingestive behaviors were not affected by 8-OH-DPAT or MET treatments in the ARC or the LH in both cycle phases. These results indicated that 5-HT1A receptors participate in the serotonergic control of feeding-related mechanisms located at the ARC and the LH. These feeding-related serotonergic circuits in both areas are possibly affected by ovarian hormones that could increase sensitivity of ARC neurons to the hypophagic effects of 8-OH-DPAT or increase the efficacy of satiety signals that terminate feeding. In addition, the present data indicated that serotonergic inputs do not exert a tonic inhibitory activity on the ARC and the LH feeding-related circuits.

Feeding behavior after metergoline or GR-46611 injections into the paraventricular nucleus of the hypothalamus in the pigeon.

The present study examined changes in spontaneous behavior of free-feeding pigeons in response to local injections of metergoline (MET, an antagonist of 5-HT(1/2) receptors; 5, 10 and 20 nmol), GR-46611 (GR, a 5-HT(1B/1D) agonist; 0.6 and 6 nmol) or vehicle into the paraventricular hypothalamic nucleus (PVN). When infused into the PVN, MET and GR promptly and reliably elicited feeding at their higher doses, without affecting drinking or non-ingestive behaviors (locomotion, exploration, preening, sleep) during the first hour after injection. Both GR- and MET-evoked ingestive responses were associated only with an increase in feeding duration, with no changes in latency to start feeding. In a second series of experiments, the effective doses of MET (20 nmol) and GR (6 nmol) were injected into other diencephalic areas. This exploratory study revealed that intense feeding responses to both MET and GR local injections are also observed in the n. medialis hypothalami posterioris and in the adjacent n. lateralis hypothalami posterioris (PMH/PLH complex, in the caudoventral hypothalamus) and in the n. magnocellularis preopticus (PPM, in the caudal preoptic region). The behavioral profiles associated with these hyperphagic responses were nucleus-specific: in the PMH/PLH, MET-induced feeding was accompanied by an increase in total feeding duration and by a reduction in the latency to start feeding, while ingestive responses evoked by MET in the PPM were associated only with an increase in feeding duration (similar to that observed in the PVN experiments). No ingestive effects were observed after intracerebroventricular (ICV, lateral ventricle) injections of MET (10, 30, 100 or 300 nmol), while ICV injections of GR (3, 15 or 30 nmol) increased feeding only at the higher dose [Da Silva RA, De Oliveira ST, Hackl LPN, Spilere CI, Faria MS, Marino-Neto J, Paschoalini MA. Ingestive behaviors and metabolic fuels after central injections of 5-HT1A and 5-HT1D/1B receptors agonists in the pigeon. Brain Res, 2004;1026:275-283]. These data indicate the presence of a tonic inhibitory influence on feeding behavior exerted by 5-HT afferents on these hypothalamic areas, and suggest that these inputs, possibly mediated by non-rodent-type 5-HT1D/1B receptors, can affect both satiety and satiation mechanisms.

An approach to evaluate the ability of rats to discriminate different levels of illumination in the plus maze test: effects of scopolamine.

Previous research has shown that the visual system is important for rats to establish the arm preference in the elevated plus maze (EPM), an animal model of anxiety. This study aims at evaluating whether a gradient of illumination between the enclosed arms of the maze (E/E(DeltaLux)) could be a reliable approach to detect drugs-induced harmful effect on visual discrimination of rats. Four EPM configurations with different E/E(DeltaLux) (8, 41 and 85lx) were used to demonstrate that as E/E(DeltaLux) increases, rats avoid to explore the light enclosed arm, which characterizes the animal ability to discriminate the most illuminated area within the protected environment of the maze. The establishment of either 41 or 85 E/E(DeltaLux) failed to alter the traditional spatial-temporal variables in the EPM. In addition, systemic treatment with midazolam (MDZ; 1.0mgkg(-1), a classical anxiolytic) induced anxiolysis in rats tested in 41 and 85 E/E(DeltaLux) EPM, with no change in the visual discrimination, when evaluated by the level of light enclosed arm exploration. Systemic treatment with scopolamine (SCP; 1.0, 2.0 and 8.0mgkg(-1)), a drug endowed with harmful properties upon the visual system, did not change either the open arm avoidance or the visual discrimination at the low doses, but induced increased light enclosed arm (visual discrimination deficit) and open arm exploration (anxiolytic like effect) at a higher dose. We propose that the incorporation of an E/E(DeltaLux) in the EPM may reinforce the predict validity of the test since it enables to evaluate whether a visual discrimination deficit can be confounded with an anxiolytic-like effect, thus establishing a false positive detection.

Ingestive effects of NMDA and AMPA-kainate receptor antagonists microinjections into the lateral hypothalamus of the pigeon (Columba livia).

This study examined the ingestive and behavioral effects of NMDA- and AMPA/kainate glutamatergic receptor blockade in the lateral hypothalamic area (LHy) of free-feeding pigeons (Columba livia). Injections of MK-801 (NMDA receptor antagonist; 6 nmol) or CNQX (AMPA/kainate receptor antagonist; 25.8 nmol) into the LHy of free-feeding pigeons induced significant increases in food intake and in feeding duration, as well as reductions in the latency to start feeding. Duration, latency and volume of water intake, as well as duration of sleep-like behavior, alert immobility, locomotion and preening were not changed by these treatments in the LHy. These results indicate that glutamatergic inputs to cells containing NMDA and/or AMPA receptors located in the LHy could modify both the beginning of a feeding bout (or the end of a period of satiety) and its duration (satiation). Our data also suggest that these inhibitory glutamatergic influences on feeding behavior are tonically active in the LHy.

Behavioral effects of 8-OH-DPAT injections into pontine and mesencephalic areas containing 5-HT-immunoreactive perikarya in the pigeon.

This study examined the distribution of 5-HT-immunoreactive perikarya (5-HT-IRp) and the effects of local injections of 8-OH-DPAT into 5-HT-IRp-containing pontine and mesencephalic regions on feeding and drinking behaviors in free-feeding pigeons. When infused into the midline 5-HT-IRp-containing areas, 8-OH-DPAT (6.1 nmol) reliably elicited drinking and, to a lesser extent, feeding responses during the first hour after injection. These responses were significantly higher than the ingestive indexes observed (1) after vehicle (ascorbic acid 0.1%, 200 nl) injections at the same sites and (2) after 8-OH-DPAT injections into adjacent sites devoid of 5-HT-IRp. Increases in drinking were proportionally higher than those observed in feeding and a significant negative correlation was observed between water and food after midline 8-OH-DPAT injections. Similar dipsogenic responses were observed after injections of different 8-OH-DPAT doses (0.6, 2.0, and 6.1 nmol). Pretreatment with local injections of p-MPPI (an antagonist of 5-HT1A receptors) attenuated the ingestive responses evoked by 8-OH-DPAT injections. Injections of 8-OH-DPAT into lateral 5-HT-IRp-containing sites evoked only inconsistent and weak ingestive responses. These results indicate that 5-HT1A receptor-mediated circuits located in the midline superior raphe system of the pigeon may play an important role in mechanisms controlling water intake, similar to that observed in mammals.

Stress-induced core temperature changes in pigeons (Columba livia).

Changes in body temperature are significant physiological consequences of stressful stimuli in mammals and birds. Pigeons (Columba livia) prosper in (potentially) stressful urban environments and are common subjects in neurobehavioral studies; however, the thermal responses to stress stimuli by pigeons are poorly known. Here, we describe acute changes in the telemetrically recorded celomatic (core) temperature (Tc) in pigeons given a variety of potentially stressful stimuli, including transfer to a novel cage (ExC) leading to visual isolation from conspecifics, the presence of the experimenter (ExpR), gentle handling (H), sham intracelomatic injections (SI), and the induction of the tonic immobility (TI) response. Transfer to the ExC cage provoked short-lived hyperthermia (10-20 min) followed by a long-lasting and substantial decrease in Tc, which returned to baseline levels 2 h after the start of the test. After a 2-hour stay in the ExC, the other potentially stressful stimuli evoked only weak, marginally significant hyperthermic (ExpR, IT) or hypothermic (SI) responses. Stimuli delivered 26 h after transfer to the ExC induced definite and intense increases in Tc (ExpR, H) or hypothermic responses (SI). These Tc changes appear to be unrelated to modifications in general activity (as measured via telemetrically recorded actimetric data). Repeated testing failed to affect the hypothermic responses to the transference to the ExC, even after nine trials and at 1- or 8-day intervals, suggesting that the social (visual) isolation from conspecifics may be a strong and poorly controllable stimulus in this species. The present data indicated that stress-induced changes in Tc may be a consistent and reliable physiological parameter of stress but that they may also show stressor type-, direction- and species-specific attributes.

Distribution of serotonin 5-HT1A-binding sites in the brainstem and the hypothalamus, and their roles in 5-HT-induced sleep and ingestive behaviors in rock pigeons (Columba livia).

Serotonin 1A receptors (5-HT1ARs), which are widely distributed in the mammalian brain, participate in cognitive and emotional functions. In birds, 5-HT1ARs are expressed in prosencephalic areas involved in visual and cognitive functions. Diverse evidence supports 5-HT1AR-mediated 5-HT-induced ingestive and sleep behaviors in birds. Here, we describe the distribution of 5-HT1ARs in the hypothalamus and brainstem of birds, analyze their potential roles in sleep and ingestive behaviors, and attempt to determine the involvement of auto-/hetero-5-HT1ARs in these behaviors. In 6 pigeons, the anatomical distribution of [(3)H]8-OH-DPAT binding in the rostral brainstem and hypothalamus was examined. Ingestive/sleep behaviors were recorded (1h) in 16 pigeons pretreated with MM77 (a heterosynaptic 5-HT1AR antagonist; 23 or 69 nmol) for 20 min, followed by intracerebroventricular ICV injection of 5-HT (N:8; 150 nmol), 8-OH-DPAT (DPAT, a 5-HT1A,7R agonist, 30 nmol N:8) or vehicle. 5-HT- and DPAT-induced sleep and ingestive behaviors, brainstem 5-HT neuronal density and brain 5-HT content were examined in 12 pigeons, pretreated by ICV with the 5-HT neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) or vehicle (N:6/group). The distribution of brainstem and diencephalic c-Fos immunoreactivity after ICV injection of 5-HT, DPAT or vehicle (N:5/group) into birds provided with or denied access to water is also described. 5-HT1ARs are concentrated in the brainstem 5-HTergic areas and throughout the periventricular hypothalamus, preoptic nuclei and circumventricular organs. 5-HT and DPAT produced a complex c-Fos expression pattern in the 5-HT1AR-enriched preoptic hypothalamus and the circumventricular organs, which are related to drinking and sleep regulation, but modestly affected c-Fos expression in 5-HTergic neurons. The 5-HT-induced ingestivebehaviors and the 5-HT- and DPAT-induced sleep behaviors were reduced by MM77 pretreatment. 5,7-DHT increased sleep per se, decreased tryptophan hydroxylase expression in the raphe nuclei and decreased prosencephalic 5-HT release but failed to affect 5-HT- or DPAT-induced drinking or sleep behavior. 5-HT- and DPAT-induced ingestive and sleep behaviors in pigeons appear to be mediated by heterosynaptic and/or non-somatodendritic presynaptic 5-HT1ARs localized to periventricular diencephalic circuits.

Adrenergic control of glycemia in the paraventricular nucleus of the hypothalamus in pigeons.

The effects of local injections of adrenaline into the paraventricular nucleus (PVN) and into other anterior hypothalamic areas on blood glucose levels were investigated in conscious pigeons (Columba livia). Adrenaline evoked a reliable and potent increase in blood glucose levels when injected into the PVN; no glycemic change was observed after vehicle injections into the PVN or after adrenaline injections into the 3rd ventricle or hypothalamic structures adjacent to the PVN. Local pretreatment with propranolol, but not with phentolamine, abolished the adrenaline-induced hyperglycemia. The present results indicate that adrenergically mediated circuits into the avian PVN play an important role in central mechanisms of energy balance that may be equivalent to those observed in mammalian species.

Feeding induced by microinjections of NMDA and AMPA-kainate receptor antagonists into ventral striatal and ventral pallidal areas of the pigeon.

The participation of glutamatergic circuits of the ventral basal ganglia in feeding-related regulatory mechanisms has been extensively indicated in primate and rodent species. In avian species, it has been shown that ICV injections of MK-801 or of CNQX increase food intake and reduce the latency of feeding initiation in free-feeding pigeons. In the present study, the effects of local injections of MK-801 (6 nmol), CNQX (160 nmol) or vehicle (0.2 microl) into a number of ventral striatopallidal nuclei on feeding, drinking and non-ingestive (sleep, preening) spontaneous behaviors were investigated in free-feeding pigeons (Columba livia). Intense feeding responses associated with an increased duration of feeding behavior were consistently recorded after injections of MK-801 or CNQX into the medial two-thirds of the tuberculum olfactorium (TO), the ventral aspect of lobus parolfactorium (LPOv), or the ventral pallidum (VP). In contrast, the latency of feeding initiation was unaffected by these treatments. No changes in drinking, preening or sleep responses were observed after drug injections into the TO/LPOv/VP area. These data indicate that glutamate-mediated circuits in the TO/LPOv/VP area can play an inhibitory role in feeding behavior in this species, contributing to the conclusion of a feeding bout, thus delaying satiation processes, and that these effects may be mediated by AMPA and NMDA receptors. Additionally, our data support the notion that a region functionally and anatomically comparable to the mammalian accumbens shell may be present in the TO/LPOv/VP region of the pigeon, and that the existence of a glutamatergic circuit in the ventral striatum controlling feeding-related phenomena may represent a highly conserved attribute throughout the amniote's evolution.

Ingestive behaviors and metabolic fuels after central injections of 5-HT1A and 5-HT1D/1B receptors agonists in the pigeon.

The effects of intracerebroventricular injections of 8-OH-DPAT (a 5-HT1A agonist; 3, 15 or 30 nmol) or GR46611 (a 5-HT1B/1D agonist; 3, 15 or 30 nmol) on feeding, drinking, preening and sleep-like behaviors were investigated in free-feeding (FF) pigeons. The effects of these 5-HT agonists on blood glucose and free fatty acids levels were also examined. Injections of 8-OH-DPAT evoked intense lipolytic and dipsogenic effects, but failed to affect feeding, non-ingestive behaviors and glycemic levels. On the other hand, GR46611 evoked significant increases in food intake (at the higher dose), as well as lipolytic and hyperglycemic effects, but left drinking and other non-ingestive behaviors unchanged. These effects are opposed to those found in rodents, and may be associated with the diverse, species-specific nature and distribution of these receptors, underscoring the need to examine the functional aspects of the 5-HT1 receptor family in a more extensive range of non-rodent species.

The behavioral satiety sequence in pigeons (Columba livia). Description and development of a method for quantitative analysis.

The postprandial event known as the specific dynamic action is an evolutionarily conserved physiological set of metabolic responses to feeding. Its behavioral counterpart, a sequence of drinking, maintenance (e.g., grooming) and sleep-like behaviors known as the behavioral satiety sequence (BSS), has been thoroughly described in rodents and has enabled the refined evaluation of potential appetite modifiers. However, the presence and attributes of a BSS have not been systematically studied in non-mammalian species. Here, we describe the BSS induced in pigeons (Columba livia) by 1) the presentation of a palatable seed mixture (SM) food to free-feeding animals (SM+FF condition) and 2) re-feeding after a 24-h fasting period (FD24h+SM), which was examined by continuous behavioral recording for 2h. We then compare these patterns to those observed in free-feeding (FF) animals. A set of graphic representations and indexes, drawn from these behaviors (latency, time-to-peak, inter-peak intervals and the first intersection between feeding curves and those of other BSS-typical behaviors) were used to describe the temporal structure and sequential relationships between the pigeon's BSS components. Cramér-von Mises-based statistical procedures and bootstrapping-based methods to compare pairs of complex behavioral curves were described and used for comparisons among the behavioral profiles during the free-feeding recordings and after fasting- and SM-induced BSS. FD24h+SM- and SM+FF-induced feeding were consistently followed by a similar sequence of increased bouts of drinking, followed by preening and then sleep, which were significantly different from that of FF birds. The sequential and temporal patterns of the pigeon's BSS were not affected by differences in food intake or by dissimilarity in motivational content of feeding stimuli. The present data indicated that a BSS pattern can be reliably evoked in the pigeon, in a chronological succession and sequence that strongly resembled that observed in rodents and primates. This pattern can be quantitatively described and compared using different suitable and coordinated behavioral measures, enabling further studies on the comparative and evolutionary aspects of the mechanisms that shape the post-consummatory behavioral flux in amniotes.

Serotonergic control of ingestive and post-ingestive behaviors in pigeons (Columba livia): the role of 5-HT1A receptor-mediated central mechanisms.

Central injections of serotonin (5-HT) produce hyperdipsic and hypnogenic behavioral effects that are correlated to decreased Fos-immunorreactivity of 5-HT neurons in free-feeding pigeons. We herein (1) probed the role of 5-HT(1A) receptors on the 5-HT- or 8-OH-DPAT-evoked postprandial behaviors and (2) described the sleep-waking states (waking, W; drowsiness, D; slow-wave sleep, SWS; rapid-eye movement sleep, REMS) and sleep architecture of free-feeding pigeons after these treatments. Latency, frequency and duration of feeding, drinking, preening, exploratory and sleep-like behaviors (SLB) were examined after intracerebroventricular (ICV) injections of 5-HT (0, 50 or 150 nmol) or 8-OH-DPAT (DPAT, 0 or 30 nmol) in pigeons pretreated with the 5-HT(1A) antagonist WAY100635 (WAY, 0, 0.1, 0.3 or 1 nmol). Additionally, the acute (1h) waking-sleep-related electrographic activity in the hippocampus (HP) was examined after ICV injections of 5-HT (150 or 300 nmol) or DPAT (30 or 60 nmol) in pigeons pretreated with WAY (0 or 1 nmol). 5-HT and DPAT acutely increased drinking and then sleep: all doses of WAY attenuated the 5-HT (50 nmol) -induced dipsogenic effect, but left unchanged the effects of the 150 nmol 5-HT dose. The WAY 0.1 nmol dose blocked the SLB induced by the 5-HT 50 nmol dose. Given before the vehicle (VEH) injections, WAY does not affect water or food intake, but increased the SLB duration at all doses. DPAT injections increased feeding, drinking and SLB. All the WAY doses attenuated the DPAT-induced drinking and feeding responses, and the WAY 0.1 and 0.3 nmol doses reduced DPAT-induced SLB. DPAT or 5-HT injections decreased the duration of electrographically-determined waking, increased the durations of D and induced the emergence of SWS and REMS states indistinguishable from the hippocampal EEG associated with spontaneous sleep, as judged from visual and spectral analysis. WAY (1 nmol) increased SWS and D, and potentiated the 5-HT- and DPAT-induced SWS. These data suggest that 5-HT-induced drinking depends on the activation of presynaptic 5-HT(1A) receptors, while 5-HT(1A) autoreceptor activation contributes to the 5-HT-induced sleep. 5-HT-induced drinking and sleep behaviors may thus be provoked by a 5-HT(1A)-evoked, rebound-like reduction in central 5-HTergic activity. These data also indicate that an ongoing, tonic and inhibitory influence of central 5-HT circuits may participate in the control of feeding, drinking and rest behaviors in pigeons during the wake, nibbling diurnal state. These mechanisms appear to be comparable to those found in mammals, suggesting that they may represent a conserved, plesiomorphic functional trait of the amniotes brain.

NMDA preconditioning attenuates cortical and hippocampal seizures induced by intracerebroventricular quinolinic acid infusion.

Searching for new therapeutic strategies through modulation of glutamatergic transmission using effective neuroprotective agents is essential. Glutamatergic excitotoxicity is a common factor to neurodegenerative diseases and acute events such as cerebral ischemia, traumatic brain injury, and epilepsy. This study aimed to evaluate behavioral and electroencephalographic (EEG) responses of mice cerebral cortex and hippocampus to subconvulsant and convulsant application of NMDA and quinolinic acid (QA), respectively. Moreover, it aimed to evaluate if EEG responses may be related to the neuroprotective effects of NMDA. Mice were preconditioned with NMDA (75 mg/kg, i.p.) and EEG recordings were performed for 30 min. One day later, QA was injected (36.8 nmol/site) and EEG recordings were performed during 10 min. EEG analysis demonstrated NMDA preconditioning promotes spike-wave discharges (SWDs), but it does not display behavioral manifestation of seizures. Animals that were protected by NMDA preconditioning against QA-induced behavioral seizures, presented higher number of SWD after NMDA administration, in comparison to animals preconditioned with NMDA that did display behavioral seizures after QA infusion. No differences were observed in latency for the first seizure or duration of seizures. EEG recordings after QA infusion demonstrated there were no differences in the number of SWD, latency for the first seizure or duration of seizures in animals pretreated with saline or in animals preconditioned by NMDA that received QA. A negative correlation was identified between the number of NMDA-induced SWD and QA-induced seizures severity. These results suggest a higher activation during NMDA preconditioning diminishes mice probability to display behavioral seizures after QA infusion.

Feeding behaviour after injection of α-adrenergic receptor agonists into the median raphe nucleus of food-deprived rats.

This study investigated the participation of median raphe nucleus (MnR) α1-adrenergic receptors in the control of feeding behaviour. The α1-adrenergic agonist phenylephrine (PHE) and α2-adrenergic agonist clonidine (CLON) (at equimolar doses of 0, 6 and 20 nmol) were injected into the MnR of: a) rats submitted to overnight fasting (18 h); or b) rats maintained with 15 g of lab chow/day for 7 days. Immediately after the drug injections, the animals were placed in the feeding chamber and feeding and non-ingestive behaviours such as grooming, rearing, resting, sniffing and locomotion were recorded for 30 min. The results showed that both doses of PHE injected into the MnR of overnight fasted animals decreased food intake accompanied by an increase in the latency to start feeding. A reduction in feeding duration was observed only after treatment of the MnR with the 20 nmol dose of PHE. Both locomotion duration and sniffing frequency increased after injection with the highest dose PHE into the MnR. Feeding frequency and the other non-ingestive behaviours remained unchanged after PHE treatment in the MnR. Both doses of PHE injected into the MnR of food-restricted rats decreased food intake. This hypophagic response was accompanied by a decrease in feeding duration only after treatment of the MnR with the highest dose of PHE. The latency to start feeding and feeding frequency were not affected by injection of either dose of PHE into the MnR. While both doses of PHE increased sniffing duration, the highest dose of PHE increased resting duration and resting frequency. Treatment with CLON into the MnR did not affect feeding behaviour in either of the food deprivation conditions. The present results indicate the inhibitory functional role of α1-adrenergic receptors within the MnR on feeding behaviour.