Mol Psychiatry: Too much pressure, teenagers don't want to socialize? Scientists have revealed that leptin may alleviate the lack of social pleasure induced by adolescent stress

Lack of pleasure is the core symptom of depression, which can be divided into physical pleasure loss and social pleasure loss, the former manifested as the loss of pleasant sensations of individual physical stimulation (food, smell, touch, etc.

For most species, socializing is a rewarding activity
.

On September 22, 2022, the Xin-Yun Lu team at Augusta University's Georgia School of Medicine revealed that leptin promotes adolescent social behavior
by promoting oxytocin synthesis in the hypothalamus.

1

Leptin enhances social location preference

In the two boxes of devices that can be freely passed, a new nest is placed on each side, and the pre-experimental puberty (6 weeks old) mice can freely shuttle in the two new nest environments, and then multiple mice are placed on the side of the A new nest, and the mice are grouped for 24 mice, and then the mice live alone on the side of the B new nest for 24 hours, and it is found that both female and male mice are willing to stay on the side of the A new litter, and there is a clear social position preference, but this position preference can be destroyed
by chronic stress.

More interestingly, mice can significantly enhance their position preference after receiving abdominal leptin injection in a social position preference test
.

Figure 1: Social preference in adolescent mice

2

Leptin promotes social isolation aversion, rather than social rewards, related to motivated behavior

The above social position preferences involve two different motivational processes
: social activity preferences (social living) and social isolation aversion (living alone).

In another experiment, the pre-experimental adolescent mice can be free to shuttle in the two A and B new nest environments, and then the mice are placed in the B new nest for 24 hours, living in the C new nest environment for 24 hours, in the test stage, the mice are in the A and B new nest environment (A environment is neutral stimulation, B environment is social isolation stimulation), the result table does not have a position preference, intraperitoneal injection of leptin can drive the mice away from the B environment, more willing to stay in the A environment, causing social isolation aversion related to the condition position preference
。

Figure 2: Leptin-driven social isolation-related aversion behavioral motivation

3

Oxytocin in the brain is a downstream target of leptin

Oxytocin in the hypothalamic paraventricular nucleus (PVN) plays a key role
in regulating social behavior.

Figure 3: Hypothalamic leptin receptor and oxytocin expression

summary

In this paper, we established social conditioned position preferences in adolescence through behavior, and found that leptin can promote conditional position preferences by enhancing motivational behaviors related to social distancing, and can effectively alleviate the lack of
social pleasure caused by adolescent stress.

Original Source:

Lei， Y.