By: Susana Pecina, Kent Berridge and Jay Schulkin
Tuesday, April 25, 2006


Nucleus accumbens CRF increases cue-triggered motivation for sucrose reward: paradoxical positive incentive effects in stress? Abstract (provisional)

Kent Berridge and Susana Pecina in BMC Biology 4:8, BioMed Central, 13 April 2006

Background

Corticotropin-releasing factor (CRF) is typically considered to mediate aversive aspects of stress, fear and anxiety. However, CRF release in the brain is also elicited by natural rewards and incentive cues, raising the possibility that some CRF systems in the brain mediate an independent function of positive incentive motivation, such as amplifying incentive salience. Here we asked whether activation of a limbic CRF subsystem magnifies the increase in positive motivation for reward elicited by incentive cues previously associated with that reward, in a way that might exacerbate cue-triggered binge pursuit of food or other incentives? We assessed the impact of CRF microinjections into the medial shell of nucleus accumbens using a pure incentive version of Pavlovian-Instrumental transfer, a measure specifically sensitive to the incentive salience of reward cues (which it separates from influences of aversive stress, stress reduction, frustration and other traditional explanations for stress-increased behavior). Rats were first trained to press one of two levers to obtain sucrose pellets, and then separately conditioned to associate a Pavlovian cue with free sucrose pellets. On test days, rats received microinjections of vehicle, CRF (250 or 500 ng/0.2 ul) or amphetamine (20 ug/0.2 ul). Lever pressing was assessed in the presence or absence of the Pavlovian cues during a half-hour test.

Results

Microinjections of the highest dose of CRF (500 ng) or amphetamine (20 ug) selectively enhanced the ability of Pavlovian reward cues to trigger phasic peaks of increased instrumental performance for a sucrose reward, each peak lasting a minute or so before decaying after the cue. Lever pressing was not enhanced by CRF microinjections in the baseline absence of the Pavlovian cue or during the presentation without a cue, showing that the CRF enhancement could not be explained as a result of generalized motor arousal, frustration or stress, or by persistent attempts to ameliorate aversive states.

Conclusions

We conclude that CRF in nucleus accumbens shell amplifies positive motivation for cued rewards, in particular by magnifying incentive salience that is attributed to Pavlovian cues previously associated with those rewards. CRF-induced magnification of incentive salience provides a novel explanation as to why stress may produce cue-triggered bursts of binge eating, drug addiction relapse, or other excessive pursuits of rewards.

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This research also appears in the following English and Spanish language publications

• EurekAlert!, April 12, 2006: Stress-induced levels of corticotropin-releasing factor responsible for binge behaviour
• NewsWise, April 13, 2006: Binge Behavior/Addiction Linked to Stress, Tripling Desire for Sugar
• MedPage Today, April 13, 2006: Addiction Relapse Associated with Temptation Brain Chemical
• ScienceDaily.com, April 14, 2006: Stress-induced Levels of Hormone Responsible for Binge Behavior
• The Michigan Daily, April 18, 2006: Experiment Shows Link Between Stress and Binge Eating

• La Opinion, April 14, 2006: Una consecuencia más del estrés
• BBC Mundo.com, April 19, 2006: ¿Estresado? ojo con las adicciones
• Terra Actualidad - April 13, 2006
• Radio Cooperative - April 13, 2006
• Infobae
• Union Radio - April 13, 2006
• La Segunda
• El Mercurio Online - April 13, 2006
• DERF
• Diario Hoy - April 13, 2006
• 24 Horas - April 16, 2006
• Observa - April 16, 2006
• El Economista
• La Cronica de Hoy
• Correo Farmaceutico
• Canarias 7