Effects of 5HT1A Activation on Depression Profile Following 5-HT Depletion in Rats Lacking Social Attachment Since Weanling

Abstract

Objective: Post weanling isolation-reared (IR) rats are featured with depressive phenotype, yet its mechanism is not clearly defined particularly in terms of the involvement of central 5-HT1A receptors. The present study aims to examine the effects of 5HT1A activation on forced swim test (FST) in IR rats following 5-HT depletion.

Methods: Social control (SOC) and IR rats received an intracerebraoventricular (ICV) injection of 5-HT depletion agent, 5,7-DHT. 14 days after the surgery, rats were assessed their performance in FST with or without the challenge with a 5-HT1A agonist, 8-OH-DPAT. Rats were then sacrificed for analyzing their 5-HT tissue levels and the expressions of their 5-HA1A receptors in prefrontal cortex (PFC), hippocampus (HPX), and amygdala (AMY).

Results: 5,7-DHT decreased the tissue concentration of 5-HT in both IR and SOC rats. IR rats were more immobile and less sensitive to the lesion-induced immobility, however this effect was reversed by acute challenge of 8-OH-DPAT. 5,7-DHT lesion increased the expression of PFC 5-HT1A receptors.

Conclusion: The integrity of central 5-HT system is developmentally crucial for the 5-HT1A-relevant depression profile in rats of social isolation.

Keywords: 5-HT1A receptors; Depression; Isolation-rearing; Serotonin.

Figure 1.

Effects of 8-OH-DPAT on locomotor activity in rats of IR and social control (SOC) (N=5, for each group). Scored as total travel distance in the 60 min activity test. Data are represented by mean±SEM. ^*p<0.05, ^**p<0.01. SEM: standard error of the mean.

Figure 2.

Effects of intracerebraoventricular (ICV) injection of 5-HT depletion agent, 5,7-DHT on the performance of forced swim test (FST) in rats of IR and social control (SOC) (N=5, for each group). Scored as (A) Immobility, (B) Swimming, and (C) Climbing of rats reared in social (SOC) or isolation (IR) conditions. Data are represented by mean±SEM. ^**p<0.01. SEM: standard error of the mean.

Figure 3.

Acute effects of 8-OH-DPAT on the performance of forced swim test (FST) in rats of IR and social control (SOC) under sham and 5,7-DHT depletion conditions (N=5, for each group). Scored as (A) Immobility, (B) Swimming, and (C) Climbing of 5,7-DHT treated rats reared in social (SOC) or isolation (IR) conditions. Data are represented by mean±SEM. ^*p<0.05, ^**p<0.01. SEM: standard error of the mean.

Figure 4.

Effects of intracerebraoventricular (ICV) injection of 5-HT depletion agent, 5,7-DHT and isolation rearing (IR) on the expressions of 5-HT1A receptors of (A) prefrontal cortex (PFC), (B) hippocampus (HPX), and (C) amygdala (AMY) in rats of IR and social control (SOC) (N=5, for each group). Data are represented by mean±SEM. SEM: standard error of the mean.