Differential Response of Central Dopaminergic System in Acute and Chronic Unpredictable Stress Models in Rats

Abstract

We aimed to evaluate the response of dopaminergic system in acute stress (AS) and chronic unpredictable stress (CUS) by measuring dopamine (DA) levels, its receptor densities in the frontal cortex, striatum, hippocampus, amygdala and orbito-frontal cortex regions of rat brain, and investigated the corresponding behavioral locomotor changes. Involvement of D(1) receptor was also examined during AS and CUS using A 68930, a D(1) selective agonist. Rats were exposed to AS (single immobilization for 150 min) and CUS (two different stressors for 7 days). AS significantly decreased the DA levels in the striatum and hippocampus, and A 68930 pretreatment significantly reverted these changes. However, in the frontal cortex significantly increased DA levels were remain unchanged following A 68930. CUS led to a decrease of DA levels in the frontal cortex, striatum and hippocampus, which were normalized by A 68930. Saturation radioligand binding assays revealed a significant decrease in the number of D(1)-like receptors in the frontal cortex during CUS, which were further decreased by A 68930 pretreatment. However, in the striatum and hippocampus, A 68930 pretreatment reduced the CUS induced increase in the number of D(1)-like receptors. No significant changes were observed in the amygdala and orbito-frontal cortex during AS and CUS, while D(2)-like receptors were unchanged in all the brain regions studied. Locomotor activity was significantly decreased in both the stress models, A 68930 pretreatment significantly increased stereotypic counts and horizontal activity. Thus, present investigation provide insights into the differential regional response of dopaminergic system during AS and CUS. Further, neurochemical and behavioral effects of D(1) agonist pretreatment suggest specific modulatory role of D(1) receptor under such stressful episodes.

Effect of acute swim stress on plasma corticosterone and brain monoamine levels in bidirectionally selected DxH recombinant inbred mouse strains differing in fear recall and extinction

“…In contrast, acute stress mostly enhanced and chronic stress decreased central dopamine and serotonin levels in a region-specific manner (Ahmad et al, 2010; Rasheed et al, 2010). In the prefrontal cortex, dopamine was increased by stressors like acute swim stress (H-FSS mice) or by acute restraint stress (Ahmad et al, 2012).…”

Neurobiology of chronic mild stress: Parallels to major depression

“…Within the frontal cortex, most studies report that CMS results in a reduction in DA and its primary metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), or a decreased turnover of DA indicative of reduced DA signaling (Sheikh et al, 2007; Rasheed et al, 2008, 2010; Ahmad et al, 2010; Shi et al, 2010; Dang et al, 2009a,b; Harro et al, 2001); [only in females (Dalla et al, 2008)]. Nonetheless, there also exist several reports of no effect of CMS on DA signaling (Tannenbaum and Anisman, 2003; Johnson and Yamamoto, 2009, 2010; Patterson et al, 2010; Haidkind et al, 2003; Di Chiara et al, 1999) and one report of increased DA levels in the frontal cortex following CMS (Yi et al, 2008).…”

Activating Effects of Chronic Variable Stress in Rats with Different Exploratory Activity: Association with Dopamine D1 Receptor Function in Nucleus Accumbens

“…Similarly, repeated immobilisation stress increases D 2 receptor binding in the NAcc when animals are single housed after stress, whereas pair-housing after stress is associated with increased D 2 binding in the dorsal striatum [71] . On the other hand, in several studies no chronic stress-associated change in the functional state of D 2 has been observed, either in the NAcc or in the dorsal striatum [55,56,63,64] . Considering the stress !…”

“…This finding is in line with studies that showed a decrease in basal extracellular dopamine levels in the NAcc shell [22,54] , a decreased number of dopamine transporter binding sites [54] as well as an increase in D 1 receptor-specific radioligand binding and V max of D 1 agonist-stimulated adenylyl cyclase in the NAcc, but not in the striatum, of animals submitted to chronic stress [54,55] . That this is a regionally specific effect is suggested by findings that neither acute nor chronic stress changed D 1 and D 2 receptor expression levels in the amygdala [56] . In contrast, chronic antidepressant administration decreases D 1 receptorspecific binding, cAMP accumulation [57][58][59] and spontaneous firing rates of dopaminergic neurons in the NAcc [60] , and elevates D 1 but not D 2 receptor gene expression in the NAcc [61] .…”