Prefrontal cortical D1 dopamine receptors modulate subcortical D2 dopamine receptor-mediated stress responsiveness

Abstract

Increased responsiveness to stress plays an important role in the manifestation of schizophrenia symptoms. Evidence indicates that the prefrontal cortex (PFC), and dopamine neurotransmission in the PFC in particular, is involved in the modulation of stress responsiveness. Decreased dopaminergic activity and loss of dopamine fibres have been reported in PFC in schizophrenia patients. Consequently, it was hypothesized that depletion of dopamine in PFC may facilitate increased stress responsiveness. Adult Sprague-Dawley rats received injections of 6-hydroxydopamine or saline bilaterally into the medial PFC (mPFC) following desipramine pretreatment to selectively deplete dopaminergic fibres. Following a 3-wk recovery period, the lesioned and control rats received injections of a D1 or D2 dopamine receptor agonist or vehicle into the mPFC and were immediately subjected to forced swimming as a stressor. Results showed that frequency of locomotion and rearing, behavioural measures indicative of increased dopaminergic activity in the nucleus accumbens (NAc), were significantly increased following stress in prefrontal cortical dopamine-depleted rats. This effect was significantly ameliorated by infusions of a D1 dopamine receptor agonist directly into the mPFC in a dose-dependent manner but not by infusion of a D2 dopamine receptor agonist. In addition, stress-induced behavioural changes in prefrontal cortical dopamine-depleted rats were significantly reduced following selective discrete infusions of a D2 dopamine receptor antagonist into the NAc shell. The results suggest that dopaminergic transmission via D1 receptors in the mPFC modulates D2 dopamine receptor-mediated stress responsiveness in the NAc, a feature that may be disrupted in schizophrenia patients.

Increased Phosphorylation of Extracellular Signal-Regulated Kinase in the Medial Prefrontal Cortex of the Single-Prolonged Stress Rats

“…However, there are some useful references related to ERK's role in emotion and cognition (Dawson and Ginty 2002;Huang and Reichardt 2001;Weeber and Sweatt 2002). Other line studies have confirmed associations of altered functions of brain neurotransmitter system with traumatic stress (Ressler and Nemeroff 2000;Horger and Roth 1996;Weiss 2007;Morilak et al 2005), and there were enhanced monoaminergic receptors in mPFC (Lauzon et al 2009;Scornaiencki et al 2009;Kruse et al 2009). These studies imply that the preventive effect of PD98059 observed in the current study may also be related to the excessive neurotransmitters.…”

The traumagenic neurodevelopmental model of psychosis revisited

“…Increased [124,125] Increased [128][129][130][131] Increase associated with severity of psychotic symptoms and neurocognitive dysfunction in ultra high-risk groups [130] Prefrontal cortical activity Decreased [126] Decreased [132][133][134] -CRH: Corticotrophin-releasing hormone; HPA: Hypothalamic-adrenal-pituitary.…”

“…In the ultra highrisk group, striatal 18 F-dopa uptake, a measure of dopamine activity, has been associated with severity of psychotic symptoms and neurocognitive dysfunction [130]. Furthermore, in line with the effects of chronic stress, dopamine activity in the prefrontal cortex appears to be reduced in individuals with a schizophrenia diagnosis [132][133][134].…”

Resilience to amphetamine in mouse models of netrin-1 haploinsufficiency: role of mesocortical dopamine

“…Evidence suggests that the abnormalities in striatal dopamine activity observed in psychopathologies such as schizophrenia and compulsive drug use are related to reciprocal dysfunctions in medial prefrontal cortex (mPFC) dopamine transmission ( Abi-Dargham et al 2009;Evans et al 2006;Goldstein and Volkow 2011;Howes and Kapur 2009;Kegeles et al 2010;Meyer-Lindenberg et al 2002;Slifstein et al 2015;Volkow and Fowler 2000). Indeed, studies in adult rodents show that dopamine activity in the mPFC inversely modulates dopamine release in the NAcc elicited by stressors and stimulant drugs and influences behavior (Banks and Gratton 1995;Beyer and Steketee 1999;Doherty and Gratton 1996;King et al 1997;Scornaiencki et al 2009;Ventura et al 2004;Vezina et al 1991). Proteins governing the development and extent of the dopamine input to the mPFC may therefore be critically involved in conferring differential vulnerability to the effects of stressors and drugs of abuse in adulthood.…”