Inhibition of Dopamine Neurons Prevents Incentive Value Encoding of a Reward Cue: With Revelations from Deep Phenotyping.

The survival of an organism is dependent on its ability to respond to cues in the environment. Such cues can attain control over behavior as a function of the value ascribed to them. Some individuals have an inherent tendency to attribute reward-paired cues with incentive motivational value, or incentive salience.

Inhibition of dopamine neurons prevents incentive value encoding of a reward cue: With revelations from deep phenotyping.

Unlabelled: The survival of an organism is dependent on their ability to respond to cues in the environment. Such cues can attain control over behavior as a function of the value ascribed to them. Some individuals have an inherent tendency to attribute reward-paired cues with incentive motivational value, or incentive salience.

Preclinical evidence to support repurposing everolimus for craving reduction during protracted drug withdrawal.

Cue-elicited drug-craving is a cardinal feature of addiction that intensifies (incubates) during protracted withdrawal. In a rat model, these addiction-related behavioral pathologies are mediated, respectively, by time-dependent increases in PI3K/Akt1 signaling and reduced Group 1 metabotropic glutamate receptor (mGlu) expression, within the ventromedial prefrontal cortex (vmPFC). Herein, we examined the capacity of single oral dosing with everolimus, an FDA-approved inhibitor of the PI3K/Akt effector mTOR, to reduce incubated cocaine-craving and reverse incubation-associated changes in vmPFC kinase activity and mGlu expression.

Endogenous glutamate within the prelimbic and infralimbic cortices regulates the incubation of cocaine-seeking in rats.

The incubation of cue-reinforced cocaine-seeking coincides with increased extracellular glutamate within the ventromedial prefrontal cortex (vmPFC). The vmPFC is comprised of two subregions that oppositely regulate drug-seeking, with infralimbic (IL) activity inhibiting, and prelimibic (PL) activity facilitating, drug-seeking. Thus, we hypothesized that increasing and decreasing endogenous glutamate within the IL would attenuate and potentiate, respectively, cue-reinforced drug-seeking behavior, with the converse effects observed upon manipulations of endogenous glutamate within the PL.