Disinhibition of the rat prelimbic cortex promotes serotonergic activation of the dorsal raphe nucleus and panicolytic-like behavioral effects

Abstract

Several studies have shown that serotonin plays a dual role in the modulation of defensive behaviors related to anxiety and panic. A major source of serotonergic projections to limbic structures responsible for this modulation is the dorsal raphe nucleus (DR). Anatomical studies indicate that the prelimbic (PL) cortex sends dense glutamatergic projections to the DR, leading to stimulation or inhibition of serotonin release in structures innervated by the DR. The objective of the present study was to investigate if GABAergic disinhibition of the PL by means of local administration of picrotoxin (PIC), a chloride channel blocker, can affect serotonergic tone and the expression of defensive behaviors related to anxiety and panic. We used the elevated T-maze model and Vogel conflict test to evaluate defensive responses associated with anxiety or panic. The results showed that intra-PL PIC caused an increase in c-Fos activation in serotonergic cells in DR subregions. Furthermore, the intra-PL injection of PIC induced a panicolytic-like effect without affecting behaviors associated with anxiety. Our findings suggest that the PL-DR pathway, through DR serotonergic stimulation, is involved in the control of panic-related behaviors by control of serotonin release in structures that modulate panic responses, such as the dorsal periaqueductal gray.

Activity of a vmPFC-DRN Pathway Corresponds With Resistance to Acute Social Defeat Stress

“…For example, serotonergic cells in dorsal and caudal DRN, an area with dense vmPFC innervation (Challis et al, 2014), can facilitate anxiety and aversion via projections to the basolateral amygdala (Hale et al, 2012;Paul et al, 2014). On the other hand, vmPFC-mediated activation of serotonergic cells within the dorsal and lateral DRN leads to inhibition of dorsal PAG (dPAG) activity and suppression of panic-like escape behavior (Yamashita et al, 2017). Thus, a vmPFC-DRN-dPAG circuit could promote proactive behaviors, such as fighting back or resisting defeat, via the serotonin-dependent, panic inhibition system (Paul et al, 2014).…”

Examining the Correlation between Acute Behavioral Manifestations of Concussion and the Underlying Pathophysiology of Chronic Traumatic Encephalopathy: A Pilot Study

“…The fiber tracts are susceptible to injury and shearing during the impact of a concussion due to their broad reaching projections [ 13 ]. Not surprisingly, this important system has been closely linked with anxiety and impulsivity [ 14 ].…”

Enhanced responsiveness to hypoxic panicogenic challenge in female rats in late diestrus is suppressed by short-term, low-dose fluoxetine: Involvement of the dorsal raphe nucleus and the dorsal periaqueductal gray

“…Cell counts were conducted at 200× magnification by an investigator blinded to the assignment of the tissue. The total number of c-Fos-immunoreactive cells (c-Fos-IR), TPH-immunoreactive neurons (TPH-IR), or c-Fos + TPH double-immunostained neurons (c-Fos + TPH-IR) in different regions of the DR was counted at four rostrocaudal levels, the divisions and coordinates of the DR and PAG based on previous studies (Spiacci et al, 2012; Vilela-Costa et al, 2019; Yamashita et al, 2017). At each level, two to three optimally stained sections were selected for counting and the counts averaged.…”