Estradiol suppresses ingestive response evoked by activation of 5-HT1A receptors in the lateral hypothalamus of ovariectomized rats.

The present study investigated the effects of estradiol (E2) on ingestive behavior after activation of 5-HT1A receptors in the lateral hypothalamus (LH) of female rats habituated to eat a wet mash diet. Ovariectomized rats treated with corn oil (OVX) or estradiol cypionate (OVX+E) received local injections into the LH of vehicle or an agonist of 5-HT1A receptors, 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT; at a dose of 6 nmol). To determine the involvement of these receptors in food intake, some animals were pretreated with N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexane carboxamide maleate (WAY-100635, a 5-HT1A receptor full antagonist, at a dose of 0.37 nmol), followed by the injection of the agonist 8-OH-DPAT or its vehicle. The results showed that the injection of 8-OH-DPAT into the LH of OVX rats significantly increased food intake, and the duration and frequency of this behavior. The pretreatment with E2 suppressed the hyperphagic response induced by 8-OH-DPAT in OVX animals. The inhibition of 5-HT1A receptors after pretreatment with WAY-100635 blocked the hyperphagic effects evoked by 8-OH-DPAT in OVX. These results indicate that the activity of LH 5-HT1A receptors could be affected by blood E2 levels.

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'.

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.