Injections of the of the α1-adrenoceptor antagonist prazosin into the median raphe nucleus increase food intake and Fos expression in orexin neurons of free-feeding rats.

Previously, we showed that the blockade of α1-adrenoreceptors in the median raphe nucleus (MnR) increased food intake in free-feeding rats, indicating that adrenergic mechanisms in the MnR participate in the regulation of food intake. However, the impact of such a pharmacological manipulation on other neural circuits related to food intake remains unknown. In the current study, we sought to identify forebrain regions which are responsive to α1-adrenergic receptor blockade and presumably involved in the modulation of the feeding response. For this purpose, we examined the induction of c-Fos immunoreactivity in forebrain structures following injections of the α1-adrenoceptor antagonist prazosin into the MnR of free-feeding rats. To determine the chemical identity of hypothalamic c-Fos-positive cells, we then conducted double-label immunohistochemistry for Fos/orexin (OX) or Fos/melanin-concentrating hormone (MCH). Finally, we combined anterograde tracing from the MnR with immunohistochemical detection of orexin. Prazosin injections into the MnR significantly increased food intake. The ingestive response was accompanied by an increase in Fos expression in the basolateral amygdala (BLA) and lateral hypothalamic area (LHA). In the LHA, Fos expression occurred in neurons expressing OX, but not MCH. Combined anterograde tracing experiments revealed that LHA OX neurons are prominently targeted by MnR axons. These findings suggest that intra-MnR injection of prazosin, via activation of orexinergic neurons in the LHA and non-orexinergic neurons in the BLA, evoked a motivational response toward food intake.

Relative luminosity in the plus maze upon the exploratory behaviour of female Wistar rats.

OBJECTIVE: This study evaluated the provision of two configuration of the Elevated Pluz-Maze (EPM) by analizing the exploratory behaviour of female Wistar rats in different phases of the estrous cycle in EPMs with different gradients of luminosity between the open and enclosed arms (O/E∆Lux). METHODS: Female Wistar rats were treated with Midazolam (MDZ, 1.0 mg.kg-1) and were tested for their exploratory behaviour in either the EPM 10 O/E∆Lux or EPM 96 O/E∆Lux. RESULTS: A multiple regression analysis indicated that the O/E∆Lux is negatively associated with the %Open arm entries and %Open arm time, suggesting that as O/E∆Lux increases, the open arm exploration decreases. The estrous cycle phase did not influence the open-arm exploration in either EPM. MDZ- induced anxiolysis was detected in 96 O/E∆Lux EPM in all phases of the EC. DISCUSSION: Results of this study suggest the importance of the O/E∆Lux to establish the arm preference in the EPM, and to preserve the predictive validity of the EPM.

Relative luminosity in the plus maze upon the exploratory behaviour of female Wistar rats / Efeito da luminosidade relativa em labirinto em cruz sobre o comportamento exploratório de fêmeas Wistar

Objective This study evaluated the provision of two configuration of the Elevated Pluz-Maze (EPM) by analizing the exploratory behaviour of female Wistar rats in different phases of the estrous cycle in EPMs with different gradients of luminosity between the open and enclosed arms (O/E∆Lux).Methods Female Wistar rats were treated with Midazolam (MDZ, 1.0 mg.kg-1) and were tested for their exploratory behaviour in either the EPM 10 O/E∆Lux or EPM 96 O/E∆Lux.Results A multiple regression analysis indicated that the O/E∆Lux is negatively associated with the %Open arm entries and %Open arm time, suggesting that as O/E∆Lux increases, the open arm exploration decreases. The estrous cycle phase did not influence the open-arm exploration in either EPM. MDZ- induced anxiolysis was detected in 96 O/E∆Lux EPM in all phases of the EC.Discussion Results of this study suggest the importance of the O/E∆Lux to establish the arm preference in the EPM, and to preserve the predictive validity of the EPM.

Objetivo Avaliar a provisão de duas configuracōes do Labirinto Elevado em Cruz (LEC) através do comportamento exploratório de ratas Wistar em diferentes fases do ciclo estral (CE) em LEC com diferentes gradientes de luminosidade entre os braços aberto e fechado (A/F∆Lux).Método Ratas Wistar foram tratadas com Midazolam (MDZ, 1.0 mg.kg-1) e foram testadas no LEC 10 A/F∆Lux ou LEC 96 A/F∆Lux.Resultados A análise de regressão múltipla indicou que o A/F∆Lux está negativamente associado com a % de entrada no braço aberto e % de tempo no braço aberto, sugerindo que no aumento do A/F∆Lux, a exploração do braço aberto diminui. A fase do CE não influenciou a exploração do braço aberto no LEC. A ansiólise induzida pelo MDZ foi demonstrada no 96 LEC A/F∆Lux em todas as fases do CE.Discussão Estes resultados sugerem a importância do A/F∆Lux para estabelecer a preferência da exploração do LEC e preservar a validade do LEC.

Ingestive and locomotor behaviours induced by pharmacological manipulation of -adrenoceptors into the median raphe nucleus.

The present study evaluated the involvement of α-adrenoceptors of the median raphe nucleus (MRN) in satiated rats, in food and water intake and motor behaviour. Control groups were treated with saline (SAL) or adrenaline (ADR), injected into the MRN seven minutes after injection of the vehicle used to solubilize the antagonists, propylene glycol (PLG) or SAL. Experimental groups were treated with an α-adrenoceptor antagonist, prazosin (α1, 20 or 40 nmol) or yohimbine (α2, 20 or 40 nmol) or phentolamine (non-selective α, 20 or 40 nmol), followed (later) by injection of ADR or SAL. Behaviour was recorded for 30 min. The injection of ADR and the blockade of α1 receptors resulted in hyperphagia whereas blocking α2 or α1 and α2 simultaneously did not change feeding behaviour. Pre-treatment with prazosin, followed by injection of ADR was not able to cause an increase in the amount of food ingested, while the higher dose of the α1 antagonist reduced the latency to start feeding. Pre-treatment with prazosin also caused hyperactivity. However, pre-treatment with phentolamine or yohimbine was able to block ADR-induced feeding. The present study supports the hypothesis that there is a tonic activation of α1-adrenoceptors in the MRN in satiated rats, which activates an inhibitory influence in areas that control food intake. Injection of ADR seems to activate α2 receptors, resulting in a decrease in the availability of endogenous catecholamines, which reduces the release of the signal that inhibits food intake, leading to hyperphagia.

Blockade of median raphe nucleus α1-adrenoceptor subtypes increases food intake in rats.

Previous studies have shown that the blockade of α1-adrenoceptors in the median raphe nucleus (MnR) of free-feeding animals increases food intake. Since there is evidence for the presence of α1A-, α1B- and α1D-adrenoceptors in the MnR of rats, this study investigated the involvement of MnR α1-adrenoceptor subtypes in the control of feeding behavior, looking for possible differences on the role of each α1-adrenoceptor in feeding. Male adult rats weighing 280-300 g with guide cannulae chronically implanted above the MnR were injected with antagonists of α1A- (RS100329, 0, 2, 4 or 20 nmol), α1B- (Rec 15/2615, 0, 2, 4 or 20 nmol) or α1D-adrenoceptor (BMY 7378, 0, 2, 4 or 20 nmol). Subsequently, behavioral evaluation of ingestive and non-ingestive parameters was monitored for 1h and the amount of food and water ingested was assessed for 4h. The highest dose (20 nmol) of RS100329 and BMY 7378 increased food intake, feeding duration and frequency, and decreased the latency to start feeding. During the second hour 2 nmol dose of Rec 15/2615 increased food intake and all doses of BMY 7378 decreased water intake. No behavioral alterations were observed during the fourth hour. The results corroborate previous work from our lab in which we describe the involvement of α1-adrenoceptors of MnR on food intake control. Moreover, we show evidence that α1A- and α1D-adrenoceptors mediate feeding responses to adrenaline injections and that the behavioral modifications are of considerable duration, persisting up to 2h after injection of the antagonists.

The microinjection of a cannabinoid agonist into the accumbens shell induces anxiogenesis in the elevated plus-maze.

This study investigated the effect of a cannabinoid agonist injected into the shell region of the nucleus accumbens (nAcb shell) on anxiety-related behaviors. The animals (male Wistar rats) were unilaterally microinjected with either ACEA (arachidonyl-2'-chloroethylamide a CB1 receptor agonist) at doses of 0.005, 0.05 or 0.5 pmol, or vehicle (ethanol 0.04% in saline 0.9%) and submitted to the elevated plus-maze (EPM), a pre-clinical test of anxiety. The data showed that rats microinjected with ACEA (0.05 pmol/0.2 µl) into the nAcb shell exhibited decreased % open arm time and open arm entries in comparison with the control group, which is compatible with an anxiogenic-like effect. To rule out the hypothesis that spread of the drug into the ventricle was responsible for the observed anxiogenic effect, 0.05 pmol ACEA was injected into the lateral ventricle and shown not to alter the responses representative of fear/anxiety and locomotion. The locomotor activity was not changed at the dose of 0.05 pmol ACEA microinjected into the nAcb shell. The present data suggest that activation of cannabinoid receptors in the nAcb shell may modulate fear/anxiety in the EPM.

Modulation of fear/anxiety responses, but not food intake, following α-adrenoceptor agonist microinjections in the nucleus accumbens shell of free-feeding rats.

This study investigated the effect of α-adrenoceptor agonists microinjected into the shell region of the accumbens nucleus (AcbSh) on feeding and anxiety-related behaviors in free-feeding rats. Male Wistar rats with a chronically implanted cannula into the AcbSh were unilaterally microinjected with either clonidine (CLON, α(2)-adrenoceptor agonist) or phenylephrine (PHEN, α(1)-adrenoceptor agonist) at the doses of 6 and 20 nmol and submitted to the elevated plus-maze (EPM), a pre-clinical test of anxiety. Immediately after the EPM test, the animals underwent food intake evaluation for 30 min. The data showed that rats microinjected with CLON (20 nmol/0.2 µl) into the AcbSh exhibited increased %Open arm time, which is compatible with an anxiolytic-like effect. The CLON-induced anxiolysis was corroborated by increased head-dipping and decreased stretched-attend posture, two ethologically derived behaviors which are fear/anxiety-motivated. The animal's locomotor activity was not changed by 20 nmol CLON microinjection into the AcbSh. However, neither dose of PHEN microinjected into the AcbSh was able to alter either the spatial-temporal or ethological variables representative of fear/anxiety and locomotion. Food intake was not altered by any dose of CLON and PHEN microinjected into the AcbSh, but the 20 nmol CLON microinjection induced increased motor activity in the feeding test. The data suggests that noradrenergic projections to the AcbSh may underlie fear/anxiety modulation through α(2)-adrenoceptor in the AcbSh, while feeding behavior was unaffected by noradrenergic modulation in the AcbSh of free-feeding rats. This article is part of a Special Issue entitled 'Anxiety and Depression'.

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.

Effects of GABA ligands injected into the nucleus accumbens shell on fear/anxiety-like and feeding behaviours in food-deprived rats.

In an attempt to establish a relationship between food intake and fear/anxiety-related behaviours, the goal of this study was to investigate the effect of bilateral injections of GABAA (Muscimol, MUS, doses 25 and 50ng/side) and GABAB (Baclofen, BAC, doses 32 and 64ng/side) receptor agonists in the nucleus accumbens shell (AcbSh) on the level of fear/anxiety-like and feeding behaviours in 24h food-deprived rats. The antagonists of GABAA (Bicuculline, BIC, doses 75 and 150ng/side) and GABAB (Saclofen, SAC, doses 1.5 and 3µg/side) were also tested. The results indicated that the total number of risk assessment behaviour decreased after the injection of both doses of GABAA agonist (MUS) into the AcbSh of 24h food-deprived rats exposed to elevated plus maze. Similar results were obtained after treatment with both doses of GABAB (BAC) agonist in the AcbSh. These data indicated that the activation of both GABAA and GABAB receptors within the AcbSh caused anxiolysis in 24h food-deprived rats. In addition, feeding behaviour (food intake, feeding latency and feeding duration) remained unchanged after treatment with both GABA agonists. In contrast, both food intake and feeding duration decreased after injections of both doses of BIC (GABAA antagonist), while the feeding latency remained unchanged after treatment with both GABA antagonists in the AcbSh of 24h food-deprived rats. The treatment with SAC (GABAB antagonist) did not affect feeding behaviour. Collectively, these data suggest that emotional changes evoked by pharmacological manipulation of the GABA neurotransmission in the AcbSh are not linked with changes in food intake.

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.

Phenylephrine into the median raphe nucleus evokes an anxiolytic-like effect in free-feeding rats but does not alter food intake in free feeding rats.

This study investigated the role of MnR α1-adrenergic receptors in the control of anxiety-like and feeding behaviors and attempted to reveal a possible functional association between both behaviors. The α1-adrenergic agonist phenylephrine (PHE) (at doses of 0.2, 2, 6, 20 nmol) or saline was injected into the MnR or into the pontine nucleus (Pn) of free-feeding rats. The animals were exposed to the elevated plus maze to analyse spatial-temporal and ethological variables. Subsequently, the ingestive and non-ingestive behaviors were recorded during 30 min and feeding and drinking behaviors were measured. Both in the elevated plus-maze and in the feeding chamber, all PHE doses injected into the MnR decreased the risk assessment frequency, an ethological parameter of anxiolytic-like effect. The spatial-temporal variables remained unchanged after PHE treatment. Feeding behavior was not affected by PHE into the MnR. The anxiety-like or ingestive behaviors were not affected by PHE treatment in the Pn, an area adjacent to the MnR. These data indicate that α1-adrenergic receptors within MnR participate in the control of anxiety-like behaviors. The absence of effects on feeding behavior after MnR α1-adrenergic activation could be due to an elevated α1-adrenergic tonus and its possible strong facilitatory influence on 5-HT neurons within MnR. Furthermore, the present results suggest that anxiety-like and feeding behaviors controled by MnR adrenergic circuits operate by independent neural pathways.

Changes in food intake and anxiety-like behaviors after clonidine injected into the median raphe nucleus.

Serotonergic neurons in the median raphe nucleus (MnR) are stimulated by alpha(1)-adrenergic agonists and inhibited by alpha(2) agonists. This study investigated the participation of MnR alpha(2)-adrenergic receptors in the control of anxiety-like behavior and feeding as an attempt to establish a functional association between these behaviors. The alpha(2)-adrenergic agonist clonidine (CLON) was injected into the MnR (0, 0.2, 2, 6, 20nmol), into the pontine nucleus (Pn) or into the mesencephalic reticular formation (mRt) (0.2, 20nmol) of free-feeding rats. The animals were exposed to the elevated plus-maze to evaluate spatial-temporal and ethological variables. Subsequently, the ingestive and non-ingestive behaviors were recorded during 30min and the quantity of food and water consumed were measured. The lowest dose of CLON injected into the MnR decreased the total risk assessment (TRA) frequency, an ethological parameter of anxiolytic-like effect, but did not change feeding behavior. The highest dose of CLON injected into the MnR increased the TRA frequency, an anxiogenic-like effect. Similar result was observed after CLON injected into the Pn and mRt at the highest dose. In addition, clonidine at the highest dose caused hyperphagy accompanied by a reduction in the latency to start eating and an increase in feeding frequency when injected into the MnR but not in the Pn or mRt. These data indicate that MnR alpha(2)-adrenergic receptors participate in the control of anxiety-like and feeding behaviors, probably decreasing the facilitatory influence on MnR serotonergic neurons. The present results suggest that these behaviors involve independent neural pathways.

WAY100635 blocks the hypophagia induced by 8-OH-DPAT in the hypothalamic nuclei.

This study examined the influence of pretreatment with N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexane carboxamide maleate (WAY100635, full 5-HT1A receptor antagonist, 37 nmol) on feeding effects evoked by local injections of 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT, 5-HT(1A) and 5-HT(7) receptor agonist, 6 nmol) into the LH and into the ARC of female rats adapted to a wet mash diet (enriched with 10% sucrose), during diestrus or estrus. The results showed that the LH-pretreatment with WAY100635 suppressed the hypophagic effects evoked by 8-OH-DPAT during estrus as well as diestrus. The ARC pretreatment with WAY100635 blockaded the hypophagia evoked by 8-OH-DPAT in estrus rats. The previous treatment with WAY100635 in the ARC also suppressed the feeding duration decrease evoked by 8-OH-DPAT in estrus. The latency to start feeding, the drinking behavior and the durations of other non-ingestive behaviors were not affected by the different treatments, hypothalamic regions (LH or ARC), and/or estrous cycle stages (diestrus and estrus), except for the locomotion duration increase after 8-OH-DAPT in LH-pretreated rats in diestrus. The present findings confirm our previous suggestion that ARC- and the LH-5-HT(1A) receptors participate in the serotonergic control of feeding and that these feeding-related serotonergic circuits in LH are affected by ovarian hormones, since the treatment with WAY100635 evoked a hypophagia response during the diestrus phases.

Arcopallium, NMDA antagonists and ingestive behaviors in pigeons.

This study investigated the effects of local injections of 6,7-dinitroquinoxaline-2,3(1H,4H)-dione (DNQX, AMPA-kainate receptor antagonist, 0.8 and 2.7 nmol) and MK-801 (NMDA receptor antagonist, 1.8 and 6.0 nmol) into the nucleus taeniae of the amygdala (TnA) and the arcopallium intermedium (AI) on ingestive and non-ingestive behaviors in free-feeding pigeons. Injections of DNQX into the TnA or into the AI failed to consistently affect feeding behavior; DNQX vehicle (DMSO) affected drinking when injected into the TnA. MK-801 injections into the AI produced a delayed increase in food and water intake. In the TnA, MK-801 increased water intake in the first two hours after the treatment. These data indicate that glutamatergic circuits in arcopallial structures in the pigeon, comparable to the mammalian medial amygdala, are involved in the inhibitory control of ingestive behaviors, suggesting that this can represent a conserved functional attribute in the amniote prosencephalon.

The peeping response of pigeons (Columba livia) to isolation from conspecifics and exposure to a novel environment.

The present study examined the acute behavioral responses of pigeons to separation from conspecifics and exposure to an unfamiliar environment (UE). The effects of (1) repeated exposure to the UE; (2) visual isolation from surroundings, or saline injections; and (3) diazepam treatment (i.p., 0.25, 0.75, 2.5 or 7.5mg/kg) before the trial were also examined. UE exposure evoked intense ballistic head movements (peeping), gradually replaced with angular head movements (AHM), both associated with immobility of the trunk and legs. These behaviors failed to habituate after three trials (7-day intertrial intervals). Visual isolation from the surroundings and saline injection prior to exposure to the UE increased the AHM and reduced peeping. Doses of diazepam (0.25 and 0.75 mg/kg) that have demonstrated anti-conflict effects in other tests did not affect the behavioral responses to the UE. Diazepam at 2.5 and 7.5mg/kg doses consistently increased time spent in immobility. These data suggest that peeping, although expressed in potentially threatening or harmful situations appears not to be a fear-motivated behavior or, alternatively, this specific behavioral response is not diazepam sensitive.

Food intake increased after injection of adrenaline into the median raphe nucleus of free-feeding rats.

The present study examined the effects of local injections of adrenaline (AD) or noradrenaline (NA) in equimolar doses (6, 20, and 60 nmol) into the median raphe nucleus (MRN) on ingestive and non-ingestive behaviors of free-feeding rats. The results showed that the treatment with AD at doses of 20 and 60 nmol increased food intake. While the hyperphagic response evoked by 60 nmol dose of AD was accompanied by a reduction of the latency to start feeding and an increase in the frequency of feeding, the 20 nmol dose of AD was unable to change these behavioral aspects of feeding response. The meal size and non-ingestive behaviors were not affected by AD treatment in the MRN. While water intake remained unchanged after the treatment with 20 nmol of AD in the MRN, this dose decreased the latency to start drinking. Feeding and drinking behaviors were not affected by treatment with NA in the MRN. These data suggest that adrenergic receptors of MRN participate in mechanisms that control food intake initiation or appetite. In addition, our results also indicate that the availability of energetic substrate could affect the adrenergic influence on MRN neurons since previous data indicated that the injection of AD into the MRN of food restricted rats decreased food intake.

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.

Systemic administration of a nitric oxide synthase inhibitor impairs fear sensitization in the plus-maze.

The aim of the present study was to evaluate the occurrence of fear sensitization in rats previously treated with an inhibitor of the NO syntheses and submitted to Trial1/Trial2 plus-maze (PM) procedure. Male Wistar rats received a systemic treatment with N(omega)-nitro-L-Arginine-methyl ester (L-NAME; 5, 10 or 50 mg kg(-1)) and were submitted to PM Trial1. In the following day the animals were re-exposed to the PM with no drug administration (Trial2). Some standards spatial-temporal measures, such as the percentage of entries (% Open arm entries) and time spent (% Open arm time) in the open arms and risk assessment frequency were recorded and used to estimate the animal level of fear sensitization in PM Trial2. The results showed that animals receiving L-NAME (50 mg kg(-1)) displayed increased % Open arm entries and % Open arm time in Trial2 in relation to the group receiving 0.9% saline, which is compatible with impaired fear/anxiety acquisition during Trial1/Trial2 PM procedure. In addition, rats treated with L-NAME (50 mg kg(-1)) exhibited low level of risk assessment in Trial2 in relation to the group treated with 0.9% saline, which indicates low level of fear/anxiety during PM re-exposure. The number of entries into the enclosed arms was not changed by any L-NAME treatment, which suggests no bias of the drug treatments on animal locomotor activity. The data suggest that NO synthesis may mediate the fear sensitization process in the PM.

The microinjection of AMPA receptor antagonist into the accumbens shell failed to change food intake, but reduced fear-motivated behaviour in free-feeding female rats.

This study investigated the effect of the AMPA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 2.5 and 5.0 nmol/side) microinjected into the core and shell sub-regions of the accumbens (Acb) nucleus, on food intake and the level of anxiety in female rats. Bilateral microinjections of CNQX (5.0 nmol/side) into the Acb shell (AP, +1.08 to +2.04), but not into the Acb core, induced an anxiolytic-like effect in relation to rats microinjected with vehicle, since the animals exhibited low level of SAP in the feeding test. The anxiolytic-like effect induced by 5.0 nmol CNQX microinjection into the Acb shell may not be ascribed to changes in the motor activity of the animals, because the frequency of locomotion, rearing and grooming remained unchanged after the drug microinjection. However, neither Acb shell nor Acb core CNQX microinjections were able to change the animals food intake along 1h feeding behaviour evaluation. Food intake remained unchanged 24h after the drug microinjections either into the Acb shell or into the Acb core. The data suggest that AMPA receptor blockade in the Acb nucleus may differentially change the ingestive and defensive behaviours in female rats.

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.