The role of nucleus accumbens shell GABA receptors on ventral tegmental area intracranial self-stimulation and a potential role for the 5-HT<sub>2C</sub>receptor

Northoff

2012

BMC Neurosci

Self Cite

BackgroundIdentification of potentially harmful stimuli is necessary for the well-being and self-preservation of all organisms. However, the neural substrates involved in the processing of aversive stimuli are not well understood. For instance, painful and non-painful aversive stimuli are largely thought to activate different neural networks. However, it is presently unclear whether there is a common aversion-related network of brain regions responsible for the basic processing of aversive stimuli. To help clarify this issue, this report used a cross-species translational approach in humans (i.e. meta-analysis) and rodents (i.e. systematic review of functional neuroanatomy).ResultsAnimal and human data combined to show a core aversion-related network, consisting of similar cortical (i.e. MCC, PCC, AI, DMPFC, RTG, SMA, VLOFC; see results section or abbreviation section for full names) and subcortical (i.e. Amyg, BNST, DS, Hab, Hipp/Parahipp, Hyp, NAc, NTS, PAG, PBN, raphe, septal nuclei, Thal, LC, midbrain) regions. In addition, a number of regions appeared to be more involved in pain-related (e.g. sensory cortex) or non-pain-related (e.g. amygdala) aversive processing.ConclusionsThis investigation suggests that aversive processing, at the most basic level, relies on similar neural substrates, and that differential responses may be due, in part, to the recruitment of additional structures as well as the spatio-temporal dynamic activity of the network. This network perspective may provide a clearer understanding of why components of this circuit appear dysfunctional in some psychiatric and pain-related disorders.

“…[81]; and see [20] for review) and some human studies (e.g. [36,37] and see [82] for review) have implicated the NAc in coding both aversive and rewarding states.…”

Section: Discussionmentioning

confidence: 99%

Common brain activations for painful and non-painful aversive stimuli

Northoff

2012

BMC Neurosci

Self Cite

“…Nonetheless, it is clear that at least some areas within the network code for multiple (even apparently opponent) processes (e.g., aversion and reward). For instance, many animal studies (e.g., Hayes et al, 2010; and see Carlezon and Thomas, 2009 for review) and some human work (Levita et al, 2009; see also Leknes and Tracey, 2008) have implicated the NAc as playing a key role in coding for both aversive and rewarding states. In addition, there are numerous cell types with various response characteristics throughout the amygdala, OFC, and ACC which may respond to the presence or anticipation of rewarding, aversive, or both types of stimuli; often in the absence of an obvious topology (Kawasaki et al, 2005; Paton et al, 2006; Morrison and Salzman, 2009; Shabel and Janak, 2009).…”

Section: Discussionmentioning

confidence: 99%

Identifying a Network of Brain Regions Involved in Aversion-Related Processing: A Cross-Species Translational Investigation

Front. Integr. Neurosci.

Northoff

2011

The ability to detect and respond appropriately to aversive stimuli is essential for all organisms, from fruit flies to humans. This suggests the existence of a core neural network which mediates aversion-related processing. Human imaging studies on aversion have highlighted the involvement of various cortical regions, such as the prefrontal cortex, while animal studies have focused largely on subcortical regions like the periaqueductal gray and hypothalamus. However, whether and how these regions form a core neural network of aversion remains unclear. To help determine this, a translational cross-species investigation in humans (i.e., meta-analysis) and other animals (i.e., systematic review of functional neuroanatomy) was performed. Our results highlighted the recruitment of the anterior cingulate cortex, the anterior insula, and the amygdala as well as other subcortical (e.g., thalamus, midbrain) and cortical (e.g., orbitofrontal) regions in both animals and humans. Importantly, involvement of these regions remained independent of sensory modality. This study provides evidence for a core neural network mediating aversion in both animals and humans. This not only contributes to our understanding of the trans-species neural correlates of aversion but may also carry important implications for psychiatric disorders where abnormal aversive behavior can often be observed.

“…Importantly, these mechanisms have been shown to be behaviourally relevant; for example, electrical self‐stimulation in rats relies on the functional integrity of the mesolimbic GABAergic network (e.g. Lassen et al ., ; Hayes et al ., ). Moreover, EEG‐based findings in humans support a major role for GABA A receptors in the functional connectivity of cortical networks (Fingelkurts et al ., ).…”

Section: Corticostriatal Gaba Pathwaysmentioning

confidence: 97%

Brain γ‐aminobutyric acid: a neglected role in impulsivity

Jupp

Sawiak

et al. 2014

Eur J of Neuroscience

The investigation of impulsivity as a core marker of several major neuropsychiatric disorders has been greatly influenced by the therapeutic efficacy of drugs that block the reuptake of dopamine and noradrenaline in the brain. As a result, research into the neural mechanisms of impulsivity has focused on the catecholamine systems as the loci responsible for the expression of impulsive behaviour and the primary mechanism of action of clinically effective drugs for attention-deficit hyperactivity disorder (ADHD). However, abnormalities in the catecholamine systems alone are unlikely to account for the full diversity and complexity of impulsivity subtypes, nor can they fully explain co-morbid brain disorders such as drug addiction. Here we review the lesser-studied role of γ-aminobutyric acid (GABA) in impulsivity, a major target of the dopaminergic and noradrenergic systems in the prefrontal cortex and striatum, and consider how abnormalities in this inhibitory neurotransmitter might contribute to several forms of impulsive behaviour in humans and experimental animals. Our analysis reveals several promising leads for future research that may help inform the development of new therapies for disorders of impulse control.