Effort Displayed During Appetitive Phase of Feeding Behavior Requires Infralimbic Cortex Activity and Histamine H1 Receptor Signaling.

María E Riveros,José L Valdés,Fernando Torrealba,María Ines Forray

doi:10.3389/fnins.2019.00577

María E Riveros, José L Valdés + Show 2 more

Open Access

https://doi.org/10.3389/fnins.2019.00577

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Abstract

The chances to succeed in goal-directed behaviors, such as food or water-seeking, improve when the subject is in an increased arousal state. The appetitive phase of these motivated behaviors is characterized by high levels of behavioral and vegetative excitation. The key decision of engaging in those particular behaviors depends primarily on prefrontal cortical areas, such as the ventromedial prefrontal cortex. We propose that the infralimbic cortex (ILC) located in the medial prefrontal cortex induces an increase in arousal during the appetitive phase of motivated behavior, and that this increase in arousal is, in turn, mediated by the activation of the brain histaminergic system, resulting in higher motivation for getting food rewards. To test this hypothesis, we conduct a progressive ratio operant conditioning to test the degree of motivation for food, while simultaneously manipulating the histaminergic system through pharmacologic interventions. We found that the behavioral responses to obtain food in hungry rats were disrupted when the ILC was inhibited through muscimol infusion, blocking brain H1 histamine receptors by intracerebroventricular infusion of pyrilamine or by satiety. In contrast, the consummatory behavior was not affected by ILC inhibition. The extracellular histamine levels in the ILC were increased in direct correlation with the degree of motivation measured in the progressive ratio test. ILC inhibition also prevented this increase in histamine levels. The rise in extracellular histamine levels during the progressive ratio test was similar (ca. 200%) during the active or the resting period of the day. However, different basal levels are observed for these two periods. Our findings suggest that increased histamine levels during this behavior are not simply explained by the awaked state, but instead, there is a motivation-related release of histamine, suggestive of a specific form of brain activation. Serotonin (another critical component of the ascending arousal system) was also tested. Interestingly, changes in levels of this neuromodulator were not detected during the progressive ratio test. In conclusion, our results suggest that ILC activation and subsequent increase in brain histamine release are both necessary for the normal performance of a motivated behavior such as feeding.

Highlights

In order to maximize advantageous actions, higher-order organisms need to display a continuous trade-off analysis of potential benefits and threats coming from the environment, along with development of the ability to balance these benefits with costs of executing actions to obtain positive reinforcers or avoid and prevent potential damage (Batten and Shoemaker, 1961)
We have reported previously that tuberomamillary nucleus (TMN) histaminergic neurons are the first component of the arousal system (AAS) to get activated during the appetitive phase of a food-related motivated behavior (Valdés et al, 2005) paralleled with an increase in locomotion, body core temperatures, and the activation of the infralimbic cortex (ILC) (Valdés et al, 2006)
In order to have a direct assessment of motivation, we evaluated the effort displayed to obtain a reinforcer in rats trained on an operant chamber

Summary

Introduction

In order to maximize advantageous actions, higher-order organisms need to display a continuous trade-off analysis of potential benefits and threats coming from the environment, along with development of the ability to balance these benefits with costs of executing actions to obtain positive reinforcers or avoid and prevent potential damage (Batten and Shoemaker, 1961). The decision to engage in an action directed to a specific goal requires a “motivated state.”. Motivation, increases the probability of performing a particular goal-directed behavior. One is direction, related to the specificity of actions that will be selected, and primarily driven by an internal state of the individual; the second is intensity, related to the vigor and persistence of the actions performed during a motivated state. The motivational intensity of behavior has been consistently linked to an increase in the thalamocortical activity (behavioral arousal) and the autonomic activity (vegetative arousal), implicating a change in the global state of brain activity (Kinomura et al, 1996; Hirata and Castro-Alamancos, 2010; Meeusen et al, 2013; Liu et al, 2015)

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