Prefrontal Cortex Modulates Desire and Dread Generated by Nucleus Accumbens Glutamate Disruption

Department of Psychology, University of Michigan, Ann Arbor, Michigan. Electronic address: .
Biological psychiatry (Impact Factor: 10.26). 09/2012; 73(4). DOI: 10.1016/j.biopsych.2012.08.009
Source: PubMed


Corticolimbic circuits, including direct projections from prefrontal cortex to nucleus accumbens (NAc), permit top-down control of intense motivations generated by subcortical circuits. In rats, localized disruptions of glutamate signaling within medial shell of NAc generate desire or dread, anatomically organized along a rostrocaudal gradient analogous to a limbic keyboard. At rostral locations in shell, these disruptions generate appetitive eating, but at caudal locations the disruptions generate progressively fearful behaviors (distress vocalizations, escape attempts, and antipredator reactions). Here, we asked whether medial prefrontal cortex can modulate intense motivations generated by subcortical NAc disruptions.

We used simultaneous microinjections in medial prefrontal cortex regions and in NAc shell to examine whether the desire or dread generated by NAc shell disruptions is modulated by activation/inhibition of three specific regions of prefrontal cortex: medial orbitofrontal cortex, infralimbic cortex (homologous to area 25 or subgenual anterior cingulate in the human), or prelimbic cortex (midventral anterior cingulate).

We found that activation of medial orbitofrontal cortex biased intense bivalent motivation in an appetitive direction by amplifying generation of eating behavior by middle to caudal NAc disruptions, without altering fear. In contrast, activation of infralimbic prefrontal cortex powerfully and generally suppressed both appetitive eating and fearful behaviors generated by NAc shell disruptions.

These results suggest that corticolimbic projections from discrete prefrontal regions can either bias motivational valence or generally suppress subcortically generated intense motivations of desire or fear.

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    • "Furthermore, our findings support the hypothesis that IL activation generally regulates or inhibits the control of subcortically generated motivational information over behavior (Richard and Berridge 2012). Indeed, Richard and Berridge (2012) found that intense motivations such as eating and fear-related behaviours generated by NAc shell glutamate disruptions were powerfully inhibited by the activation of IL. LaLumiere et al. (2012) further showed that IL and NAc shell interact bidirectionally in regulating cocaine-seeking behavior, in that the activation of IL inhibited reinstatement, while activation of DA neurons in the NAc shell promoted cocaine-seeking behavior after extinction. "
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    • "Besides its role in positive emotions, the NAcSh has also been indicated in negative motivational states, such as fear, defensive behavior and especially stress (Reynolds and Berridge, 2001). Studies showed that many neurotransmitters (e.g., dopamine, glutamate, 5-hydroxytryptamine (5-HT) and γ -aminobutyric acid (GABA)) within the NAcSh mediated these negative motivations (Inoue et al., 1994; Reynolds and Berridge, 2001; Richard and Berridge, 2013). Our present study found that orexin signaling in the NAcSh, including OX1R and OX2R, is also a part of the neural mechanism of which the NAcSh participates in stress-related behaviors. "
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