Elsevier

Neuroscience

Volume 196, 24 November 2011, Pages 80-96
Neuroscience

Cognitive, Behavioral, and Systems Neuroscience
Research Paper
A food predictive cue must be attributed with incentive salience for it to induce c-fos mRNA expression in cortico-striatal-thalamic brain regions

https://doi.org/10.1016/j.neuroscience.2011.09.004Get rights and content

Abstract

Cues associated with rewards acquire the ability to engage the same brain systems as rewards themselves. However, reward cues have multiple properties. For example, they not only act as predictors of reward capable of evoking conditional responses (CRs), but they may also acquire incentive motivational properties. As incentive stimuli they can evoke complex emotional and motivational states. Here we sought to determine whether the predictive value of a reward cue is sufficient to engage brain reward systems, or whether the cue must also be attributed with incentive salience. We took advantage of the fact that there are large individual differences in the extent to which reward cues are attributed with incentive salience. When a cue (conditional stimulus, CS) is paired with delivery of food (unconditional stimulus, US), the cue acquires the ability to evoke a CR in all rats; that is, it is equally predictive and supports learning the CS–US association in all. However, only in a subset of rats is the cue attributed with incentive salience, becoming an attractive and desirable incentive stimulus. We used in situ hybridization histochemistry to quantify the ability of a food cue to induce c-fos mRNA expression in rats that varied in the extent to which they attributed incentive salience to the cue. We found that a food cue induced c-fos mRNA in the orbitofrontal cortex, striatum (caudate and nucleus accumbens), thalamus (paraventricular, intermediodorsal and central medial nuclei), and lateral habenula, only in rats that attributed incentive salience to the cue. Furthermore, patterns of “connectivity” between these brain regions differed markedly between rats that did or did not attribute incentive salience to the food cue. These data suggest that the predictive value of a reward cue is not sufficient to engage brain reward systems—the cue must also be attributed with incentive salience.

Highlights

▶Individuals respond differently to reward cues. ▶Reward cues can act as predictors and/or incentive stimuli. ▶What brain regions are engaged when a cue has incentive vs. predictive value? ▶The predictive value of a reward cue is not sufficient to engage brain reward systems. ▶Brain reward systems are only engaged when reward cues are incentive stimuli.

Section snippets

Subjects

Male Sprague–Dawley rats (Charles River, Wilmington, MA, USA) weighing 250–300 g upon arrival were used. Rats were housed individually in hanging acrylic cages (8×8×9 cm3) and kept on a 12-h light/dark cycle (lights on at 0800 h) in a temperature- and humidity-controlled colony room. Food and water were available ad libitum for the duration of the study. Procedures were approved by the University Committee on the Use and Care of Animals.

Pavlovian conditioning

Pavlovian training was conducted using an autoshaping

Pavlovian conditioning

Rats were classed as STs or GTs based on their PCA score averaged over the last two days of Pavlovian training (days 6 and 7). Rats with an average approach index of ≥0.3 were designated STs (n=6, average PCA score=+0.6) and those with an index score of ≤−0.3 were designated GTs (n=10, average PCA score=−0.8). Rats with an “intermediate” score were not utilized for this study. Rats in the UN group had a PCA score of ≤0.5 or ≥−0.5 (i.e. did not show a strong preference for either the lever-CS or

Discussion

It is well established that mesocorticolimbic and cortico-striatal-thalamic brain regions that form a so-called “motive circuit” are engaged in response to cues associated with natural rewards (food, sex) and drugs of abuse (Childress et al., 1999, Kalivas and Volkow, 2005, Kelley et al., 2005a), and even to reward cues presented outside of conscious awareness (Childress et al., 2008). Together, these brain regions mediate the integration of learning, emotion, and arousal to produce motivated

Conclusions

In conclusion, it is well known that cues associated with food or drug rewards can exert powerful effects on emotions and behavior and can evoke a motivational state of “craving” or “wanting” (Childress et al., 1999, Robinson and Berridge, 2000; Brody et al., 2002, Berridge and Robinson, 2003). Individuals who attribute reward cues with incentive salience find it more difficult to resist such cues and are thereby more susceptible to disorders of impulse control such as overeating and addiction.

Acknowledgments

We would like to thank James Dell'Orco for technical assistance with the behavioral studies and James Beals, Sharon Burke and Jennifer Fitzpatrick for assistance with the in situ hybridization studies and analysis. We would also like to thank Dr. Fan Meng for assistance with statistics. We thank Kent Berridge, Paul Meyer and Ben Saunders for comments on an earlier version of the manuscript. This research was supported by National Institute of Health grant R37-DA04294 to T.E.R.

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