Metabotropic glutamate receptor blockade in nucleus accumbens shell shifts affective valence towards fear and disgust.

Glutamatergic inputs to the nucleus accumbens (NAc) modulate both appetitive and fearful motivation. It has been suggested that pathological disturbances of glutamate signaling in NAc contribute to motivation disorders, ranging from excessive desire in drug addiction to paranoia in schizophrenia. Metabotropic glutamate receptors are of special interest, as metabotropic Group II receptor (mglu2/3) agonists have been proposed as potential treatments for both addiction and schizophrenia. Here we tested whether local mglu2/3 receptor blockade in the medial shell of the rat NAc can generate intense distortions of motivation or affect, which might model clinical dysfunction. We found that microinjection of the mglu2/3 antagonist LY341495 at sites throughout medial shell suppressed appetitive motivation to eat and drink. Simultaneously, LY341495 microinjections generated fearful motivation in the form of defensive treading or burying. To assess whether the valence shift extended into a parallel hedonic shift from affective 'liking' to 'disliking' we employed the taste reactivity test, which measures affective orofacial reactions to the sensory pleasure or displeasure of tastes. We found that LY341495 microinjections reduced positive 'liking' reactions to sucrose and enhanced 'disliking' reactions. Overall, mglu2/3 antagonism at most shell sites produced a similar valence shift from positive to negative. This pattern comprised (i) generation of fearful behaviors, and (ii) induction of aversive affective reactions, together with (iii) loss of appetitive ingestion and (iv) loss of 'liking' for rewards. These results are discussed in terms of implications for clinical disorders and the influence of corticolimbic glutamate inputs to NAc in the generation of motivation and affect.