Regulation of dopamine system responsivity and its adaptive and pathological response to stress

Abstract

Although, historically, the norepinephrine system has attracted the majority of attention in the study of the stress response, the dopamine system has also been consistently implicated. It has long been established that stress plays a crucial role in the pathogenesis of psychiatric disorders. However, the neurobiological mechanisms that mediate the stress response and its effect in psychiatric diseases are not well understood. The dopamine system can play distinct roles in stress and psychiatric disorders. It is hypothesized that, even though the dopamine (DA) system forms the basis for a number of psychiatric disorders, the pathology is likely to originate in the afferent structures that are inducing dysregulation of the DA system. This review explores the current knowledge of afferent modulation of the stress/DA circuitry, and presents recent data focusing on the effect of stress on the DA system and its relevance to psychiatric disorders.

Depletion of nucleus accumbens dopamine leads to impaired reward and aversion processing in mice: Relevance to motivation pathologies

“…Also in rat, in the absence of prior IS, 6-OHDA NAcc DA depletion decreased operant (lever press) escape-avoid behaviour; furthermore, in intact subjects, performing this operant behaviour led to increased NAcc DA release (McCullough et al, 1993). Rats exposed to IS and exhibiting a high level of 2-way escape failure were characterised by a decrease in the proportion of active DA neurons in the VTA (Belujon and Grace, 2015).…”

Mesocorticolimbic dopamine functioning in primary psychopathy: A source of within-group heterogeneity

“…Conversely, ventral hippocampal glutamatergic afferents into the striatum can excite inhibitory efferents to the ventral pallidum thereby dampening pallidal GABAergic projections and thus releasing VTA DA neurons from constant inhibition, ultimately boosting the population activity of striatal DA neurons (see figure 3) (Floresco et al, 2001(Floresco et al, , 2003Lodge andGrace, 2006, Grace et al, 2007;Lisman et al, 2008;Grace, 2010;Lodge and Grace, 2011). The hippocampus and amygdala thereby interactively control the population activity of VTA DA neurons by providing an excitatory versus inhibitory influence respectively (Belujon and Grace, 2015). [INSERT FIGURE 3] Figure 3 legend: Modulatory influences on VTA neuron population activity (also see Belujon and Grace, 2015) .…”

“…The ventral pallidum serves as a global inhibitory module for VTA DA neurons through a continuous GABAergic inhibition of the VTA, thereby hyperpolarizing nearly half of all VTA DA neurons (Floresco et al, 2001;Grace et al, 2007;Grace, 2010). These ventral pallidal GABAergic projections to the VTA can be excited by glutamatergic input from basolateral amygdala which consequently dampens DA population activity (see figure 3) (Belujon and Grace, 2015). Conversely, ventral hippocampal glutamatergic afferents into the striatum can excite inhibitory efferents to the ventral pallidum thereby dampening pallidal GABAergic projections and thus releasing VTA DA neurons from constant inhibition, ultimately boosting the population activity of striatal DA neurons (see figure 3) (Floresco et al, 2001(Floresco et al, , 2003Lodge andGrace, 2006, Grace et al, 2007;Lisman et al, 2008;Grace, 2010;Lodge and Grace, 2011).…”

“…The hippocampus and amygdala thereby interactively control the population activity of VTA DA neurons by providing an excitatory versus inhibitory influence respectively (Belujon and Grace, 2015). [INSERT FIGURE 3] Figure 3 legend: Modulatory influences on VTA neuron population activity (also see Belujon and Grace, 2015) . The ventral pallidum (VP) continuously dampens VTA DA output.…”

The dopaminergic response to acute stress in health and psychopathology: A systematic review

“…Moreover, possibly through gamma-aminobutyric acid neurons, prefrontal glutamate (Kegeles et al, 2000;Moghaddam, 2002;Poels et al, 2014) and prefrontal and brainstem norepinephrine (Belujon and Grace, 2015;Cabib and Puglisi-Allegra, 2012) release may modulate stress-related cortical and striatal DAergic activity. Finally, the endogenous opioid system is involved in both physical (Bencherif et al, 2002;Zubieta et al, 2001) and psychological stress (Hsu et al, 2015;Hsu et al, 2013) and administration of a μ-opioid receptor agonist affects both cortical and subcortical DAergic activity Hagelberg et al, 2002a).…”