Ventral pallidum (VP) is centrally positioned within mesocorticolimbic reward circuits, and its dense projection to ventral tegmental area (VTA) regulates neuronal activity there. However, VP is a heterogeneous structure, and how this complexity affects its role within wider reward circuits is unclear. Here we demonstrate that projections to VTA from rostral (RVP), but not caudal VP (CVP) are robustly Fos-activated during cue-induced reinstatement of cocaine seeking—a rat model of relapse in addiction. Moreover, designer receptor-mediated transient inactivation of RVP neurons, their terminals in VTA, or functional connectivity between RVP and VTA dopamine neurons blocks the ability of drug-associated cues (but not a cocaine prime) to reinstate cocaine seeking. In contrast, CVP neuronal inhibition instead blocked cocaine-primed, but not cue-induced reinstatement. This novel double dissociation in VP sub-regional roles in drug seeking is likely important for understanding mesocorticolimbic circuits underlying reward seeking and addiction.
The release of EAAs is closely linked to the release of structural amino acids and may thus reflect nonspecific development of membrane micropores, rather than presynaptic neuronal vesicular exocytosis. The magnitude of EAA release in patients with focal contusions and ischemic events may be sufficient to exacerbate neuronal damage, and these patients may be the best candidates for treatment with glutamate antagonists in the future.
The prefrontal cortex occupies the anterior portion of the frontal lobes and is thought to be one of the most complex anatomical and functional structures of the mammalian brain. Its major role is to integrate and interpret inputs from cortical and sub-cortical structures and use this information to develop purposeful responses that reflect both present and future circumstances. This includes both action-oriented sequences involved in obtaining rewards and inhibition of behaviors that pose undue risk or harm to the individual. Given the central role in initiating and regulating these often complex cognitive and behavioral responses, it is no surprise that alcohol has profound effects on the function of the prefrontal cortex. In this chapter, we review the basic anatomy and physiology of the prefrontal cortex and discuss what is known about the actions of alcohol on the function of this brain region. This includes a review of both the human and animal literature including information on the electrophysiological and behavioral effects that follow acute and chronic exposure to alcohol. The chapter concludes with a discussion of unanswered questions and areas needing further investigation.
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