Abstract
Previous findings from this laboratory demonstrate: (1) that different classes of addictive drugs require intact norepinephrine (NE) transmission in the medial pre Frontal Cortex (mpFC) to promote conditioned place preference and to increase dopamine (DA) tone in the nucleus accumbens shell (NAc Shell); (2) that only food-restricted mice require intact NE transmission in the mpFC to develop conditioned preference for a context associated with milk chocolate; and (3) that food-restricted mice show a significantly larger increase of mpFC NE outflow then free fed mice when experiencing the palatable food for the first time. In the present study we tested the hypothesis that only the high levels of frontal cortical NE elicited by the natural reward in food restricted mice stimulate mesoaccumbens DA transmission. To this aim we investigated the ability of a first experience with milk chocolate to increase DA outflow in the accumbens Shell and c-fos expression in striatal and limbic areas of food–restricted and ad-libitum fed mice. Moreover, we tested the effects of a selective depletion of frontal cortical NE on both responses in either feeding group. Only in food-restricted mice milk chocolate induced an increase of DA outflow beyond baseline in the accumbens Shell and a c-fos expression larger than that promoted by a novel inedible object in the nucleus accumbens. Moreover, depletion of frontal cortical NE selectively prevented both the increase of DA outflow and the large expression of c-fos promoted by milk chocolate in the NAc Shell of food-restricted mice. These findings support the conclusion that in food-restricted mice a novel palatable food activates the motivational circuit engaged by addictive drugs and support the development of noradrenergic pharmacology of motivational disturbances.
Highlights
Dysfunctional processing of motivationally salient stimuli has been proposed as trans-diagnostic phenotype of behavioral disturbances (Robinson and Berridge, 2001; Kapur et al, 2005; Sinha and Jastreboff, 2013; Winton-Brown et al, 2014; Nusslock and Alloy, 2017)
The results indicate no effects of medial pre Frontal Cortex (mpFC) NE depletion on either DA or NE in the NAc Shell
MC-induced c-fos expression in the NAc Shell larger than that elicited by a novel inedible object; (3) in the Dorsomedial Striatum (DMS) of FF mice and in mpFC NE-depleted food-restriction regimen (FR) mice a novel inedible object promoted c-fos expression larger than that promoted by the palatable food; and (4) both FF and FR mice developed conditioned preference for MC-paired context when the other was associated with habitual food, only FR mice developed preference for the compartment paired with the palatable food when the other was associated with object novelty
Summary
Dysfunctional processing of motivationally salient stimuli has been proposed as trans-diagnostic phenotype of behavioral disturbances (Robinson and Berridge, 2001; Kapur et al, 2005; Sinha and Jastreboff, 2013; Winton-Brown et al, 2014; Nusslock and Alloy, 2017). Dopamine (DA) transmission in the Nucleus Accumbens Shell (NAc Shell) plays a paramount role in motivation (Di Chiara and Bassareo, 2007; Cabib and Puglisi-Allegra, 2012; Berridge and Kringelbach, 2015), severe impairment of NAc DA transmission does not always prevent development or expression of motivated responses (Nader et al, 1997). DA and opioids are independently involved in food motivation depending on the organism’s state (Bechara and van der Kooy, 1992; Baldo et al, 2013; Fields and Margolis, 2015). These findings support the involvement of different brain circuits in motivation and suggest the hypothesis that dysfunctional motivation could be associated to engagement of a specific brain circuit
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
