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.

Tonic serotonergic control of ingestive behaviours in the pigeon (Columba livia): the role of the arcopallium.

This study examined the acute changes in feeding and drinking behaviours of free-feeding and free-drinking pigeons, in response to local injections of metergoline (MET, 5-HT(1/2) receptor antagonist; 7 and 20 nmol), GR46611 (GR, 5-HT(1B/1D) agonist; 2 and 6 nmol) or vehicle, into two components of the arcopallium: the nucleus taeniae of the amygdala (TnA) and the arcopallium intermedium (AI). In the TnA, the highest MET dose elicited a short-lived hyperphagy, without affecting drinking or non-ingestive behaviours during the first hour after injection. In contrast, all MET doses promptly increased drinking when injected in the AI, without affecting feeding; this effect was still evident 3 and 24 h after the treatment. When injected in the TnA, the highest GR dose promptly increased both food and water intake; these effects persisted 24 h after the treatments. GR injections in the AI evoked long-lasting increases in drinking, but not in feeding. Injections of these drugs into other arcopallial nuclei evoked no significant ingestive effects. These data indicate the presence of a tonic inhibitory influence of serotonergic inputs, partially mediated by 5-HT(1B/1D) receptors, on feeding- and drinking-related TnA circuits and on mechanisms controlling drinking in the AI. Compared to data from the rodent medial amygdala, our results suggest that a tonic inhibitory 5-HTergic control of feeding (but not drinking) behaviour, mediated by 5-HT(1/2) receptors and exerted in the medial amygdaloid area, may represent a broadly conserved functional attribute in the amniote brain, but probably involves many important taxa-specific neural mechanisms.

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.

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.

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.

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.

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.