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1.
Behav Processes ; 213: 104966, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37981247

RESUMO

Frustration is an aversive emotion triggered by unexpected reward downshifts. Using the consummatory successive negative contrast (cSNC) task, a 32-to-2% sucrose downshift was shown to initially suppress consummatory behavior. Such suppression was followed by behavioral recovery over subsequent sessions. Individual differences often emerge in the rate of recovery after the initial consummatory suppression. These experiments were designed to determine whether a stable trait of sensation/novelty seeking (SNS) is related to such individual differences in recovery from reward downshift. In Experiment 1, open field (OF) activity in the central area served as a measure of SNS. A week later, animals received training in the cSNC task involving ten 5-min sessions of access to 32% sucrose followed by four sessions of access to 2% sucrose. Higher OF activity predicted greater consummatory suppression after downshift, but a steeper recovery rate across downshifted sessions. Controls not exposed to the OF showed cSNC, but downshifted animals performed at equivalent levels whether they had OF exposure or not. In Experiment 2, after a 32-to-2% sucrose downshift, fast vs. slow recovery animals displayed similar levels of central activity in the OF. In Experiment 3, animals exhibited similar levels of central activity whether after a 32-to-2% or an 8-to-2% sucrose downshift. In both experiments, activity levels were similar whether immediately after session 12 (onset of recovery) or after session 15 (fully recovered). These results suggest that individual variations in recovery from reward downshift are correlated with levels of SNS as a stable trait.


Assuntos
Comportamento Consumatório , Recompensa , Ratos , Animais , Feminino , Ratos Wistar , Emoções , Sacarose
2.
Science ; 382(6669): 399-404, 2023 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-37883550

RESUMO

Sexual, parental, and aggressive behaviors are central to the reproductive success of individuals and species survival and thus are supported by hardwired neural circuits. The reproductive behavior control column (RBCC), which comprises the medial preoptic nucleus (MPN), the ventrolateral part of the ventromedial hypothalamus (VMHvl), and the ventral premammillary nucleus (PMv), is essential for all social behaviors. The RBCC integrates diverse hormonal and metabolic cues and adjusts an animal's physical activity, hence the chance of social encounters. The RBCC further engages the mesolimbic dopamine system to maintain social interest and reinforces cues and actions that are time-locked with social behaviors. We propose that the RBCC and brainstem form a dual-control system for generating moment-to-moment social actions. This Review summarizes recent progress regarding the identities of RBCC cells and their pathways that drive different aspects of social behaviors.


Assuntos
Hipotálamo , Comportamento Social , Animais , Agressão/fisiologia , Hipotálamo/citologia , Hipotálamo/fisiologia , Comportamento Sexual/fisiologia , Masculino , Feminino , Comportamento Materno/fisiologia , Comportamento Paterno/fisiologia , Comportamento Consumatório
3.
Elife ; 122023 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-37555578

RESUMO

Head-fixed behavioral experiments in rodents permit unparalleled experimental control, precise measurement of behavior, and concurrent modulation and measurement of neural activity. Here, we present OHRBETS (Open-Source Head-fixed Rodent Behavioral Experimental Training System; pronounced 'Orbitz'), a low-cost, open-source platform of hardware and software to flexibly pursue the neural basis of a variety of motivated behaviors. Head-fixed mice tested with OHRBETS displayed operant conditioning for caloric reward that replicates core behavioral phenotypes observed during freely moving conditions. OHRBETS also permits optogenetic intracranial self-stimulation under positive or negative operant conditioning procedures and real-time place preference behavior, like that observed in freely moving assays. In a multi-spout brief-access consumption task, mice displayed licking as a function of concentration of sucrose, quinine, and sodium chloride, with licking modulated by homeostatic or circadian influences. Finally, to highlight the functionality of OHRBETS, we measured mesolimbic dopamine signals during the multi-spout brief-access task that display strong correlations with relative solution value and magnitude of consumption. All designs, programs, and instructions are provided freely online. This customizable platform enables replicable operant and consummatory behaviors and can be incorporated with methods to perturb and record neural dynamics in vivo.


Assuntos
Condicionamento Operante , Recompensa , Camundongos , Animais , Condicionamento Operante/fisiologia , Comportamento Animal , Sacarose , Comportamento Consumatório
4.
Nat Commun ; 14(1): 1486, 2023 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-36932069

RESUMO

For survival, it is crucial for eating behaviours to be sequenced through two distinct seeking and consummatory phases. Heterogeneous lateral hypothalamus (LH) neurons are known to regulate motivated behaviours, yet which subpopulation drives food seeking and consummatory behaviours have not been fully addressed. Here, in male mice, fibre photometry recordings demonstrated that LH leptin receptor (LepR) neurons are correlated explicitly in both voluntary seeking and consummatory behaviours. Further, micro-endoscope recording of the LHLepR neurons demonstrated that one subpopulation is time-locked to seeking behaviours and the other subpopulation time-locked to consummatory behaviours. Seeking or consummatory phase specific paradigm revealed that activation of LHLepR neurons promotes seeking or consummatory behaviours and inhibition of LHLepR neurons reduces consummatory behaviours. The activity of LHLepR neurons was increased via Neuropeptide Y (NPY) which acted as a tonic permissive gate signal. Our results identify neural populations that mediate seeking and consummatory behaviours and may lead to therapeutic targets for maladaptive food seeking and consummatory behaviours.


Assuntos
Fome , Receptores para Leptina , Camundongos , Masculino , Animais , Receptores para Leptina/genética , Receptores para Leptina/metabolismo , Hipotálamo/metabolismo , Neurônios/metabolismo , Comportamento Consumatório , Leptina/metabolismo
5.
Genes Brain Behav ; 21(7): e12827, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35878875

RESUMO

ProSAAS is a neuroendocrine protein that is cleaved by neuropeptide-processing enzymes into more than a dozen products including the bigLEN and PEN peptides, which bind and activate the receptors GPR171 and GPR83, respectively. Previous studies have suggested that proSAAS-derived peptides are involved in physiological functions that include body weight regulation, circadian rhythms and anxiety-like behavior. In the present study, we find that proSAAS knockout mice display robust anxiety-like behaviors in the open field, light-dark emergence and elevated zero maze tests. These mutant mice also show a reduction in cued fear and an impairment in fear-potentiated startle, indicating an important role for proSAAS-derived peptides in emotional behaviors. ProSAAS knockout mice exhibit reduced water consumption and urine production relative to wild-type controls. No differences in food consumption and overall energy expenditure were observed between the genotypes. However, the respiratory exchange ratio was elevated in the mutants during the light portion of the light-dark cycle, indicating decreased fat metabolism during this period. While proSAAS knockout mice show normal circadian patterns of activity, even upon long-term exposure to constant darkness, they were unable to shift their circadian clock upon exposure to a light pulse. Taken together, these results show that proSAAS-derived peptides modulate a wide range of behaviors including emotion, metabolism and the regulation of the circadian clock.


Assuntos
Neuropeptídeos/metabolismo , Animais , Ansiedade/genética , Ritmo Circadiano/genética , Comportamento Consumatório , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Peptídeos , Receptores Acoplados a Proteínas G
6.
Behav Neurosci ; 136(6): 551-560, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35771511

RESUMO

The medial frontal cortex (MFC) in rodents emits rhythmic activity that is entrained to the animal's licking cycle during consumption and encodes the value of consumed fluids. These signals are especially prominent in the rostral half of the MFC. This region is located above an orbitofrontal region where mu-opioid receptors regulate intake and reversible inactivation reduces behavioral measures associated with the incentive value and palatability of liquid sucrose. Here, we examined the effects of reversible inactivation and stimulation of mu-opioid receptors in rostral MFC on behavior in an incentive contrast licking task. Adult male rats licked to receive access to liquid sucrose, which alternated between high (16%) and low (4%) values over 30 s periods. Bilateral infusion of muscimol reduced the total number of licks over the 30 min test sessions, the time spent actively consuming sucrose, and the ratio of licks for the higher and lower value fluids. Inactivation did not alter licking frequency or variability or microstructural measures such as the duration of licking bouts that are classically associated with the palatability of a liquid reward. Infusions of [d-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin (DAMGO; 1 µg/µL) at the same sites had inconsistent behavioral effects across different subjects. Our findings suggest that the rostral MFC has a distinct role in the control of consummatory behavior and contributes to persistent consumption and not to the expression of palatability. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Assuntos
Comportamento Consumatório , Lobo Frontal , Ratos , Masculino , Animais , Ratos Sprague-Dawley , Lobo Frontal/fisiologia , Receptores Opioides mu/metabolismo , Sacarose , Ala(2)-MePhe(4)-Gly(5)-Encefalina/farmacologia , Ala(2)-MePhe(4)-Gly(5)-Encefalina/metabolismo
7.
Psychopharmacology (Berl) ; 239(5): 1563-1578, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35266035

RESUMO

RATIONALE: Adolescent cannabinoid exposure has been shown to alter cognitive, reward-related, and motor behaviors as well as mesocorticolimbic dopamine (DA) function in adult animals. Pain is also influenced by mesocorticolimbic DA function, but it is not known whether pain or cannabinoid analgesia in adults is altered by early exposure to cannabinoids. OBJECTIVE: To determine whether adolescent Δ9-tetrahydrocannabinol (THC) exposure alters pain-related behaviors before and after induction of persistent inflammatory pain, and whether it influences antinociceptive of THC, in adult rats, and to compare the impact of adolescent THC exposure on pain to its effects on known DA-dependent behaviors such as exploration and consumption of a sweet solution. METHODS: Vehicle or THC (2.5 to 10 mg/kg s.c.) was administered daily to male and female rats on post-natal day (PND) 30-43. In adulthood (PND 80-88), sensitivity to mechanical and thermal stimuli before and after intraplantar injection of complete Freund's adjuvant (CFA) was determined. Antinociceptive, exploratory, and consummatory effects of 2.0 mg/kg THC were then examined. RESULTS: Adolescent THC exposure did not significantly alter adult sensitivity to non-noxious or noxious stimuli either before or after CFA injection, nor did it alter the antinociceptive effect of THC. In contrast, adolescent THC exposure altered adult exploratory and consummatory behaviors in a sex-dependent manner: when tested as adults, adolescent THC-treated males showed less hedonic drinking than adolescent vehicle-treated males, and females but not males that had been THC-exposed as adolescents showed reduced sensitivity to THC-induced suppression of activity and THC-induced hedonic drinking as adults. CONCLUSIONS: Adolescent THC exposure that altered both exploratory and consummatory behaviors in adults did not alter pain-related behaviors either before or after induction of inflammatory pain, suggesting that cannabinoid exposure during adolescence is not likely to substantially alter pain or cannabinoid analgesia in adulthood.


Assuntos
Dronabinol , Dor , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Animais , Comportamento Consumatório , Dopamina , Feminino , Masculino , Dor/tratamento farmacológico , Ratos
8.
Pharmacol Biochem Behav ; 213: 173320, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34990705

RESUMO

Assessing the role of cannabinoid (CB) receptors in behavior is relevant given the trend toward the legalization of medicinal and recreational marijuana. The present research aims at bridging a gap in our understanding of CB-receptor function in animal models of frustrative nonreward. These experiments were designed to (1) determine the effects of chronic administration of the nonselective CB1-receptor agonist WIN 55,212-2 (WIN) on reward downshift in rats and (2) determine whether the effects of chronic WIN were reducible to acute effects. In Experiment 1, chronic WIN (7 daily injections, 10 mg/kg, ip) accelerated the recovery of consummatory behavior after a 32-to-4% sucrose downshift relative to vehicle controls. In addition, chronic WIN eliminated the preference for an unshifted lever when the other lever was subject to a 12-to-2 pellet downshift in free-choice trials, but only in animals with previous experience with a sucrose downshift. In Experiment 2, acute WIN (1 mg/kg, ip) reduced consummatory behavior, but did not affect recovery from a 32-to-4% sucrose downshift. The antagonist SR 141716A (3 mg/kg, ip) also failed to interfere with recovery after the sucrose downshift. In Experiment 3, acute WIN administration (1 mg/kg, ip) did not affect free-choice behavior after a pellet downshift, although it reduced lever pressing and increased magazine entries relative to vehicle controls. The effects of chronic WIN on frustrative nonreward were not reducible to acute effects of the drug. Chronic WIN treatment in rats, like chronic marijuana use in humans, seems to increase resistance to the effects of frustrative nonreward.


Assuntos
Benzoxazinas/farmacologia , Agonistas de Receptores de Canabinoides/farmacologia , Comportamento Consumatório/efeitos dos fármacos , Morfolinas/farmacologia , Naftalenos/farmacologia , Receptores de Canabinoides/metabolismo , Animais , Antagonistas de Receptores de Canabinoides/farmacologia , Comportamento de Escolha/efeitos dos fármacos , Condicionamento Operante/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar , Recompensa , Rimonabanto/farmacologia , Sacarose/farmacologia
9.
Pharmacol Res Perspect ; 10(1): e00907, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34962108

RESUMO

Muscarinic acetylcholine receptors (mAChRs) have been shown to mediate alcohol consumption and seeking. Both M4 and M5 mAChRs have been highlighted as potential novel treatment targets for alcohol use disorders (AUD). Similarly, M1 mAChRs are expressed throughout reward circuitry, and their signaling has been implicated in cocaine consumption. However, whether the same effects are seen for alcohol consumption, or whether natural reward intake is inadvertently impacted is still unknown. To determine the role of M1 mAChRs in alcohol consumption, we tested operant self-administration of alcohol under both fixed ratio (FR3) and progressive ratio (PR3-4) schedules. Enhancing M1 mAChR signaling (via the M1 PAM-Agonist PF-06767832, 1 mg/kg, i.p.) reduced operant alcohol consumption on a fixed schedule but had no effect on motivation to acquire alcohol. To determine whether these actions were specific to alcohol, we examined the effects of M1 enhancement on natural reward (sucrose) self-administration. Systemic administration of PF-06767832 (1 mg/kg, i.p.) also reduced operant sucrose self-administration, suggesting the actions of the M1 receptor may be non-selective across drug and natural rewards. Finally, to understand whether this reduction extended to natural consummatory behaviors, we assessed home cage standard chow and water consumption. M1 enhancement via systemic PF-06767832 administration reduced food and water consumption. Together our results suggest the M1 PAM-agonist, PF-06767832, non-specifically reduces consummatory behaviors that are not associated with motivational strength for the reward. These data highlight the need to further characterize M1 agonists, PAMs, and PAM-agonists, which may have varying degrees of utility in the treatment of neuropsychiatric disorders including AUD.


Assuntos
Consumo de Bebidas Alcoólicas/metabolismo , Comportamento Consumatório/efeitos dos fármacos , Ácidos Picolínicos/farmacologia , Receptor Muscarínico M1/metabolismo , Tiazóis/farmacologia , Alcoolismo/fisiopatologia , Alcoolismo/terapia , Animais , Masculino , Ratos , Receptor Muscarínico M1/agonistas , Recompensa , Autoadministração , Sacarose/administração & dosagem
11.
Neuropharmacology ; 201: 108836, 2021 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-34648771

RESUMO

Alcohol use disorder (AUD) constitutes a major burden to global health. Recently, the translational success of animal models of AUD has come under increased scrutiny. Efforts to refine models to gain a more precise understanding of the neurobiology of addiction are warranted. Appetitive responding for ethanol (seeking) and its consumption (taking) are governed by distinct neurobiological mechanisms. However, consumption is often inferred from appetitive responding in operant ethanol self-administration paradigms, preventing identification of distinct experimental effects on seeking and taking. In the present study, male Long-Evans, Wistar, and Sprague-Dawley rats were trained to lever press for ethanol using a lickometer-equipped system that precisely measures both appetitive and consummatory behavior. Three distinct operant phenotypes emerged during training: 1) Drinkers, who lever press and consume ethanol; 2) Responders, who lever press but consume little to no ethanol; and 3) Non-responders, who do not lever press. While the prevalence of each phenotype differed across strains, appetitive and consummatory behavior was similar across strains within each phenotype. Appetitive and consummatory behaviors were significantly correlated in Drinkers, but not Responders. Analysis of drinking microstructure showed that greater consumption in Drinkers relative to Responders is due to increased incentive for ethanol rather than increased palatability. Importantly, withdrawal from chronic ethanol exposure resulted in a significant increase in appetitive responding in both Drinkers and Responders, but only Drinkers exhibited a concomitant increase in ethanol consumption. Together, these data reveal important strain differences in appetitive and consummatory responding for ethanol and uncover the presence of distinct operant phenotypes.


Assuntos
Consumo de Bebidas Alcoólicas/psicologia , Alcoolismo/psicologia , Comportamento Apetitivo/fisiologia , Comportamento Aditivo/psicologia , Comportamento Animal/fisiologia , Condicionamento Operante/fisiologia , Comportamento Consumatório/fisiologia , Comportamento de Procura de Droga/fisiologia , Etanol/administração & dosagem , Fenótipo , Autoadministração/psicologia , Animais , Modelos Animais de Doenças , Masculino , Ratos Long-Evans , Ratos Sprague-Dawley , Ratos Wistar
12.
Elife ; 102021 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-34505830

RESUMO

This study examined how the medial frontal (MFC) and orbital frontal (OFC) cortices process reward information. We simultaneously recorded local field potentials in the two areas as rats consumed liquid sucrose rewards. Both areas exhibited a 4-8 Hz 'theta' rhythm that was phase-locked to the lick cycle. The rhythm tracked shifts in sucrose concentrations and fluid volumes, demonstrating that it is sensitive to differences in reward magnitude. The coupling between the rhythm and licking was stronger in MFC than OFC and varied with response vigor and absolute reward value in the MFC. Spectral analysis revealed zero-lag coherence between the cortical areas, and found evidence for a directionality of the rhythm, with MFC leading OFC. Our findings suggest that consummatory behavior generates simultaneous theta range activity in the MFC and OFC that encodes the value of consumed fluids, with the MFC having a top-down role in the control of consumption.


Assuntos
Comportamento Consumatório , Lobo Frontal/fisiologia , Recompensa , Ritmo Teta , Animais , Sacarose na Dieta/administração & dosagem , Eletroencefalografia , Potenciais Evocados , Preferências Alimentares , Masculino , Ratos Long-Evans , Ratos Sprague-Dawley , Fatores de Tempo
13.
Nat Commun ; 12(1): 2811, 2021 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-33990558

RESUMO

The supramammillary region (SuM) is a posterior hypothalamic structure, known to regulate hippocampal theta oscillations and arousal. However, recent studies reported that the stimulation of SuM neurons with neuroactive chemicals, including substances of abuse, is reinforcing. We conducted experiments to elucidate how SuM neurons mediate such effects. Using optogenetics, we found that the excitation of SuM glutamatergic (GLU) neurons was reinforcing in mice; this effect was relayed by their projections to septal GLU neurons. SuM neurons were active during exploration and approach behavior and diminished activity during sucrose consumption. Consistently, inhibition of SuM neurons disrupted approach responses, but not sucrose consumption. Such functions are similar to those of mesolimbic dopamine neurons. Indeed, the stimulation of SuM-to-septum GLU neurons and septum-to-ventral tegmental area (VTA) GLU neurons activated mesolimbic dopamine neurons. We propose that the supramammillo-septo-VTA pathway regulates arousal that reinforces and energizes behavioral interaction with the environment.


Assuntos
Neurônios Dopaminérgicos/fisiologia , Hipotálamo Posterior/citologia , Hipotálamo Posterior/fisiologia , Animais , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologia , Comportamento Consumatório/efeitos dos fármacos , Comportamento Consumatório/fisiologia , Dopamina/fisiologia , Feminino , Ácido Glutâmico/fisiologia , Imageamento por Ressonância Magnética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Modelos Neurológicos , Vias Neurais/citologia , Vias Neurais/fisiologia , Optogenética , Ratos , Ratos Wistar , Reforço Psicológico , Septo do Cérebro/citologia , Septo do Cérebro/efeitos dos fármacos , Septo do Cérebro/fisiologia , Área Tegmentar Ventral/citologia , Área Tegmentar Ventral/fisiologia , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiônico/administração & dosagem
14.
Science ; 372(6537)2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33795431

RESUMO

Culture can be defined as all that is learned from others and is repeatedly transmitted in this way, forming traditions that may be inherited by successive generations. This cultural form of inheritance was once thought specific to humans, but research over the past 70 years has instead revealed it to be widespread in nature, permeating the lives of a diversity of animals, including all major classes of vertebrates. Recent studies suggest that culture's reach may extend also to invertebrates-notably, insects. In the present century, the reach of animal culture has been found to extend across many different behavioral domains and to rest on a suite of social learning processes facilitated by a variety of selective biases that enhance the efficiency and adaptiveness of learning. Far-reaching implications, for disciplines from evolutionary biology to anthropology and conservation policies, are increasingly being explored.


Assuntos
Comportamento Animal , Invertebrados , Comportamento Social , Vertebrados , Animais , Evolução Biológica , Mimetismo Biológico , Comportamento Consumatório , Evolução Cultural , Cultura , Hereditariedade , Humanos , Invertebrados/genética , Invertebrados/fisiologia , Aprendizagem , Comportamento de Utilização de Ferramentas , Vertebrados/genética , Vertebrados/fisiologia , Vocalização Animal
15.
Psychopharmacology (Berl) ; 238(3): 691-697, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33410982

RESUMO

BACKGROUND: Reduced motivation is one of the main symptomatic features of inflammation-induced depression. However, the exact nature of inflammation-induced alterations in motivation remains to be fully defined. As inflammation has been shown to increase sensitivity to negative stimuli, the present series of experiments was initiated to determine whether systemic inflammation induced by infra-septic doses of lipopolysaccharide (LPS) in mice influences consummatory and instrumental responding to successive negative contrast. METHODS: Successive negative contrast was operationally defined by a shift to a lower value reward than the one mice were trained with. Mice were trained to drink a high sucrose concentration solution and exposed to an acute shift to a lower concentration of sucrose. In another series of experiments, mice were trained to nose poke for chocolate pellets according to a fixed reinforcement schedule 10 (10 nose pokes for the food reinforcement) and exposed to a shift to a lower reward value (decreased number of chocolate pellets or replacement of chocolate pellets by less preferred grain pellets). Lipopolysaccharide (LPS) was administered at the dose of 0.33 1 mg/kg 24 h before the shift. RESULTS: Mice trained to drink a high sucrose concentration responded to the shift in reward value by a reduction in the volume of sucrose consumed and a decrease in lick numbers and bout durations. Mice trained to nose poke for chocolate pellets responded to the shift by alterations in their total number of nose pokes. In both conditions, LPS had no consistent effect on the response to the shift in reward value. CONCLUSIONS: These findings indicate a high variability in the effects of LPS on successive negative contrast and fail to provide evidence in favor of the hypothesis that LPS increases sensitivity to decreases in expected rewards.


Assuntos
Condicionamento Operante/efeitos dos fármacos , Comportamento Consumatório/efeitos dos fármacos , Inflamação/psicologia , Lipopolissacarídeos/farmacologia , Reforço Psicológico , Sacarose/farmacologia , Animais , Chocolate , Alimentos , Masculino , Camundongos , Motivação/efeitos dos fármacos , Esquema de Reforço , Recompensa , Sacarose/administração & dosagem
16.
Physiol Behav ; 229: 113279, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33285178

RESUMO

Glucagon-like peptide-1 (GLP-1) is an incretin hormone that is essential for the regulation of food intake and approved for the treatment of type 2 diabetes mellitus and obesity in humans. More recently, GLP-1 has been investigated for its ability to modulate motivation for food and drugs. Reward behavior can be divided into two components: 'motivational' (i.e., approach and consummatory behaviors) and 'affective' (i.e., perceived palatability). Studies show that GLP-1 analogs reduce the motivation to approach and consume palatable food, but the impact on affective responding is unknown. Thus, the present study tested the effect of the GLP-1 analog, Exendin-4 (Ex-4), on the appetitive response to intraorally delivered sucrose and quinine. Results showed that Ex-4 (2.4ug/kg ip) failed to alter passive drip, appetitive reactions (i.e., mouth movements, tongue protrusions, and lateral tongue protrusions) or aversive reactions (i.e., gapes) to sucrose. Paw-licking, however, was significantly reduced by Ex-4. Treatment with Ex-4 also failed to influence passive drip to quinine, but increased the latency to gape and reduced the total number of gapes emitted. In addition, Ex-4 reduced intake of quinine in water restricted rats, but did not reduce conditioned aversion (i.e., gapes) or avoidance (i.e., reduced intake) of a LiCl-paired saccharin cue. Thus, while Ex-4 had no effect on a learned aversion, it reduced approach and ingestion of sweet and bitter solutions, while leaving the appetitive affective response to the sweet almost intact, and the aversive affective response to the bitter reduced. Treatment with Ex-4, then, differentially modulates appetitive and consummatory components of reward, depending on the valence of the stimulus and whether its valence is learned or innate.


Assuntos
Diabetes Mellitus Tipo 2 , Peptídeo 1 Semelhante ao Glucagon , Animais , Comportamento Apetitivo , Comportamento Consumatório , Ratos , Recompensa , Paladar
17.
Nat Neurosci ; 23(10): 1253-1266, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32747789

RESUMO

Maintaining healthy body weight is increasingly difficult in our obesogenic environment. Dieting efforts are often overpowered by the internal drive to consume energy-dense foods. Although the selection of calorically rich substrates over healthier options is identifiable across species, the mechanisms behind this choice remain poorly understood. Using a passive devaluation paradigm, we found that exposure to high-fat diet (HFD) suppresses the intake of nutritionally balanced standard chow diet (SD) irrespective of age, sex, body mass accrual and functional leptin or melanocortin-4 receptor signaling. Longitudinal recordings revealed that this SD devaluation and subsequent shift toward HFD consumption is encoded at the level of hypothalamic agouti-related peptide neurons and mesolimbic dopamine signaling. Prior HFD consumption vastly diminished the capacity of SD to alleviate the negative valence associated with hunger and the rewarding properties of food discovery even after periods of HFD abstinence. These data reveal a neural basis behind the hardships of dieting.


Assuntos
Núcleo Arqueado do Hipotálamo/fisiologia , Comportamento Consumatório/fisiologia , Dieta Hiperlipídica , Preferências Alimentares/fisiologia , Neurônios/fisiologia , Área Tegmentar Ventral/fisiologia , Proteína Relacionada com Agouti/fisiologia , Animais , Dopamina/fisiologia , Feminino , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Vias Neurais/fisiologia , Optogenética
18.
Psychoneuroendocrinology ; 119: 104718, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32535402

RESUMO

Growth hormone secretagogue receptor (GHSR), the receptor for ghrelin, is expressed in key brain nuclei that regulate food intake. The dopamine (DA) pathways have long been recognized to play key roles mediating GHSR effects on feeding behaviors. Here, we aimed to determine the role of GHSR in DA neurons controlling appetitive and consummatory behaviors towards high fat (HF) diet. For this purpose, we crossed reactivable GHSR-deficient mice with DA transporter (DAT)-Cre mice, which express Cre recombinase under the DAT promoter that is active exclusively in DA neurons, to generate mice with GHSR expression limited to DA neurons (DAT-GHSR mice). We found that DAT-GHSR mice show an increase of c-Fos levels in brain areas containing DA neurons after ghrelin treatment, in a similar fashion as seen in wild-type mice; however, they did not increase food intake or locomotor activity in response to systemically- or centrally-administered ghrelin. In addition, we found that satiated DAT-GHSR mice displayed both anticipatory activity to scheduled HF diet exposure and HF intake in a binge-like eating protocol similar to those in wild-type mice, whereas GHSR-deficient mice displayed impaired responses. We conclude that GHSR expression in DA neurons is sufficient to both mediate increased anticipatory activity to a scheduled HF diet exposure and fully orchestrate binge-like HF intake, but it is insufficient to restore the acute orexigenic or locomotor effects of ghrelin treatment. Thus, GHSR in DA neurons affects appetitive and consummatory behaviors towards HF diet that take place in the absence of caloric needs.


Assuntos
Comportamento Consumatório/fisiologia , Dieta Hiperlipídica , Comportamento Alimentar/fisiologia , Receptores de Grelina/fisiologia , Animais , Regulação do Apetite/genética , Comportamento Animal/fisiologia , Neurônios Dopaminérgicos/metabolismo , Ingestão de Alimentos/genética , Ingestão de Alimentos/fisiologia , Preferências Alimentares/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Receptores de Grelina/genética , Receptores de Grelina/metabolismo
19.
J Neurosci ; 40(24): 4727-4738, 2020 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-32354856

RESUMO

Decades of research have shown that the NAc is a critical region influencing addiction, mood, and food consumption through its effects on reinforcement learning, motivation, and hedonic experience. Pharmacological studies have demonstrated that inhibition of the NAc shell induces voracious feeding, leading to the hypothesis that the inhibitory projections that emerge from the NAc normally act to restrict feeding. While much of this work has focused on projections to the lateral hypothalamus, the role of NAc projections to the VTA in the control food intake has been largely unexplored. Using a retrograde viral labeling technique and real-time monitoring of neural activity with fiber photometry, we find that medial NAc shell projections to the VTA (mNAc→VTA) are inhibited during food-seeking and food consumption in male mice. We also demonstrate that this circuit bidirectionally controls feeding: optogenetic activation of NAc projections to the VTA inhibits food-seeking and food intake (in both sexes), while optogenetic inhibition of this circuit potentiates food-seeking behavior. Additionally, we show that activity of the NAc to VTA pathway is necessary for adaptive inhibition of food intake in response to external cues. These data provide new insight into NAc control over feeding in mice, and contribute to an emerging literature elucidating the role of inhibitory midbrain feedback within the mesolimbic circuit.SIGNIFICANCE STATEMENT The medial NAc has long been known to control consummatory behavior, with particular focus on accumbens projections to the lateral hypothalamus. Conversely, NAc projections to the VTA have mainly been studied in the context of drug reward. We show that NAc projections to the VTA bidirectionally control food intake, consistent with a permissive role in feeding. Additionally, we show that this circuit is normally inactivated during consumption and food-seeking. Together, these findings elucidate how mesolimbic circuits control food consumption.


Assuntos
Comportamento Consumatório/fisiologia , Ingestão de Alimentos/fisiologia , Núcleo Accumbens/fisiologia , Área Tegmentar Ventral/fisiologia , Animais , Condicionamento Operante/fisiologia , Masculino , Camundongos , Atividade Motora/fisiologia , Vias Neurais/fisiologia , Optogenética , Recompensa
20.
PLoS One ; 15(4): e0231654, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32340024

RESUMO

In marine environments, tropical and subtropical habitats are considered to be inherently less productive than more temperate systems. As such, foraging site fidelity among vertebrate predators occupying low-latitude marine systems is generally low as a response to an increased unpredictability of resources. We investigated the foraging movements of Masked Boobies breeding on Middle Cay, Jamaica using GPS loggers to examine if the presence of a nearby bathymetric feature influenced foraging site fidelity in a tropical system, the Caribbean Sea. According to the movements of tracked individuals, this population of boobies shows a high degree of spatial fidelity in foraging site selection, concentrated on the northern edge of Pedro Bank. We suggest this feature as an important location for marine conservation in the region and demonstrate its utility to foraging boobies via habitat modeling using a maximum entropy approach of relevant habitat variables. Finally, we place this study into the global context of Masked Booby foraging by examining the published literature of relevant tracking studies for population-level similarity in foraging metrics. According to hierarchical clustering of foraging effort, Masked Boobies demonstrate a density-dependent response to foraging effort regardless of colony origin or oceanic basin consistent with the principles of Ashmole's Halo.


Assuntos
Aves/fisiologia , Comportamento Consumatório , Comportamento Espacial , Animais , Ecossistema , Espécies em Perigo de Extinção , Jamaica , Movimento
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