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.

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.

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, 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.

GABAA and GABAB agonist microinjections into medial accumbens shell increase feeding and induce anxiolysis in an animal model of anxiety.

This study investigated the effect of GABAA (muscimol, MUSC) and GABAB (baclofen, BACL) agonist receptors microinjected into medial accumbens shell on feeding and the level of fear in free-feeding rats submitted to the elevated plus-maze (EPM), an animal model of anxiety. Bilateral microinjections of either MUSC (128 pmol/0.2 microl/side) or BACL (128 and 256 pmol/0.2 microl/side) induced an anxiolytic-like effect since they decreased the occurrence of risk assessment, a defensive behaviour positively correlated with the animal anxiety level. Bilateral BACL microinjection (128 pmol), but not MUSC, also increased the head-dipping frequency over the open arms of the EPM, another representative behaviour of anxiety, but negatively correlated with it. In addition to anxiolysis, the present study also showed that the microinjection of MUSC and BACL agonists into rostral sites of the medial Acb shell (AP, +1.2 to +1.6) increased food intake significantly whereas drinking behaviour kept unchanged. Both doses of MUSC and BACL also decreased feeding latency. BACL but not MUSC dose-dependently increased food length. The data indicated a putative role of GABA receptors (especially GABAB) in the medial Acb shell for anxiety modulation in rats.

The effects of metabolic stress and vagotomy on emotional learning in an animal model of anxiety.

The aim of the present study is to evaluate the role of the blood glucose (BG) level in emotional learning in the elevated plus maze (EPM), an animal model of anxiety. In Experiment 1, male Wistar rats were submitted to different EPM trial lengths (1- or 5-min). Blood samples were withdrawn before and after the maze exploration, through a polyethylene cannula chronically implanted into the jugular vein. In Experiment 2, the animals received either saline or 2-deoxy-D-glucose, a glucoprivic drug (2-DG, 250 or 500 mg kg(-1)) by i.p. route, 30 min before a 5-min EPM exposure and were retested in the maze (Trial1/Trial2 EPM procedure) 24 h later. In an independent group of rats, blood samples were withdrawn 0, 5, 15, and 30 min after 2-DG administration, through the jugular vein, to determine BG. In Experiment 3, the animals underwent a vagotomy and were tested in a Trial1/Trial2 EPM procedure four weeks later. The results showed that rats exploring the EPM for 5 min displayed increased fear and higher hyperglycemia than those exploring the EPM for 1 min. In addition, rats submitted to 5-min EPM Trial1 length displayed higher level of fear on Trial2, as well as higher percentage of shortening of the %Open arm entries and %Open arm time from Trial1 to Trial2, which characterizes the occurrence of emotional learning. In contrast, rats previously vagotomized or treated with 2-DG (500 mg kg(-1)) showed the same level of fear on both EPM trials and a low percentage of shortening, from Trial1 to Trial2, of the %Open arm entries and %Open arm time, indicating poor emotional learning. The data is discussed regarding the role of glycaemia in emotional learning in the EPM.

The gradient of luminosity between open/enclosed arms, and not the absolute level of Lux, predicts the behaviour of rats in the plus maze.

The effect of the gradient of luminosity between the open and the enclosed arms (O/E(DeltaLux)) of the elevated plus maze (EPM), upon the level of fear/anxiety in rats submitted to the trial 1/trial 2 paradigm was investigated. Male Wistar rats were assigned to freely explore either of three EPM configuration, with the enclosed arm walls constructed with either translucent glass (O/E(DeltaLux)=11), opaque glass (O/E(DeltaLux)=96) or wood (O/E(DeltaLux)=141), for 2 consecutive days (trial 1/trial 2). Independently of the EPM configuration, rats exhibited increased fear during trial 2 relative to trial 1, thus indicating that the level of O/E(DeltaLux), at least in the range used here, is not a determinant variable for the establishment of increased anxiety induced by prior maze experience. The groups tested under 11 and 141 O/E(DeltaLux) were those who exhibited the low and higher level of open arm avoidance, respectively. There was also an increased open arms avoidance over trial 1 in rats tested under 11 and 96 O/E(DeltaLux), only. These results suggest that the enclosed arm preference of rats during trial 1 EPM procedure may be changed by the level of O/E(DeltaLux) of the test. The present results are discussed with respect to the controversy regarding the role of luminosity on EPM performance.