D1 receptors regulate dendritic morphology in normal and stressed prelimbic cortex

Abstract

Both stress and dysfunction of prefrontal cortex are linked to psychological disorders, and structure and function of medial prefrontal cortex (mPFC) are altered by stress. Chronic restraint stress causes dendritic retraction in the prelimbic region (PL) of mPFC in rats. Dopamine release in mPFC increases during stress, and chronic administration of dopaminergic agonists results in dendritic remodeling. Thus, stress-induced alterations in dopaminergic transmission in PL may contribute to dendritic remodeling. We examined the effects of dopamine D1 receptor (D1R) blockade in PL during daily restraint stress on dendritic morphology in PL. Rats either underwent daily restraint stress (3 h/day, 10 days) or remained unstressed. In each group, rats received daily infusions of either the D1R antagonist SCH23390 or vehicle into PL prior to restraint; unstressed and stressed rats that had not undergone surgery were also examined. On the final day of restraint, rats were euthanized and brains were processed for Golgi histology. Pyramidal neurons in PL were reconstructed and dendritic morphology was quantified. Vehicle-infused stressed rats demonstrated dendritic retraction compared to unstressed rats, and D1R blockade in PL prevented this effect. Moreover, in unstressed rats, D1R blockade produced dendritic retraction. These effects were not due to attenuation of the HPA axis response to acute stress: plasma corticosterone levels in a separate group of rats that underwent acute restraint stress with or without D1R blockade were not significantly different. These findings indicate that dopaminergic transmission in mPFC during stress contributes directly to the stress-induced retraction of apical dendrites, while dopamine transmission in the absence of stress is important in maintaining normal dendritic morphology.

Effects of repeated yohimbine administration on reinstatement of palatable food seeking: involvement of dopamine D1-like receptors and food-associated cues

“…Interestingly, we found that when the D 1 R antagonist SCH-23390 was combined with repeated yohimbine administration the effect on body weight was attenuated. This parallels findings from a recent study by Lin et al (2014) showing that intra-prelimbic infusions of SCH-23390 during repeated restraint stress (3 h/day × 10 days) reduced several indices of chronic stress, including attenuation of weight gain, increases in adrenal weight, and dendritic retraction in prelimbic cortex. Thus, yohimbine appears to have induced a form of stress that is similar in some ways to that of other, non-pharmacological, stressors.…”

Chronic restraint stress causes a delayed increase in responding for palatable food cues during forced abstinence via a dopamine D1-like receptor-mediated mechanism

“…This interpretation, however, is unlikely given that a) there was a robust decrease in weight gain in the SCH + Stressed group, similar to that observed in the Vehicle + Stressed group, b) the difference in adrenal weights 2 days after stress in the SCH + Stressed versus SCH + Unstressed groups is very similar to that seen in the Vehicle groups, and c) there is evidence that intra-medial PFC injections of SCH-23390 do not alter the HPA axis response to restraint stress as measured by plasma corticosterone concentrations [28]. Thus, it appears that SCH-23390 did not reduce the “stressfulness” of the manipulation.…”

“…In a recent report by Lin et al [28], microinjections of SCH-23390 into the prelimbic region of medial PFC during chronic restraint reversed this dendritic retraction. Given that medial PFC is a critical node in the circuitry of relapse to palatable food seeking [16, 39] it is possible that D 1 R-mediated structural changes in this region due to chronic stress contributed to the increased food seeking observed in the present study.…”

Differential effects of stress on microglial cell activation in male and female medial prefrontal cortex

“…For instance, dopamine mediates effects of stress on cortical structure and function in males (Rey et al, 2014; Lin et al, 2015) and dopaminergic innervation of mPFC is sexually dimorphic in young adult rats (Kritzer and Creutz, 2008). Notably, microglia express receptors for most neurotransmitters, including dopamine (Domercq et al, 2013), and can respond to and modulate neurotransmitter signaling.…”