Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Social Interactions of DAT-HET Epi-Genotypes Differing for Maternal Origins: The Development of a New Preclinical Model of Socio-Sexual Apathy

Version 1 : Received: 14 May 2021 / Approved: 18 May 2021 / Online: 18 May 2021 (10:01:33 CEST)

How to cite: Brancato, A.; Lo Russo, S.; Liberati, A.S.; Carbone, C.; Zelli, S.; Laviola, G.; Cannizzaro, C.; Adriani, W. Social Interactions of DAT-HET Epi-Genotypes Differing for Maternal Origins: The Development of a New Preclinical Model of Socio-Sexual Apathy. Preprints 2021, 2021050404 (doi: 10.20944/preprints202105.0404.v1). Brancato, A.; Lo Russo, S.; Liberati, A.S.; Carbone, C.; Zelli, S.; Laviola, G.; Cannizzaro, C.; Adriani, W. Social Interactions of DAT-HET Epi-Genotypes Differing for Maternal Origins: The Development of a New Preclinical Model of Socio-Sexual Apathy. Preprints 2021, 2021050404 (doi: 10.20944/preprints202105.0404.v1).

Abstract

Social interaction is essential for life and is impaired in many psychiatric disorders like schizophrenia, au-tism, depression and major anxiety disorder. Monoamine transmission plays a key role in social behavior and both genetic and epigenetic modifications of dopamine and noradrenaline neurotransmission-related genes can affect the levels of social interaction. Since heterozygous individuals for a specific genetic trait possess only one mutant allele of that trait, in order to better evaluate the role of the interaction between genetics and epigenetics in unmasking latent genetically-determined predispositions, our interest has focused on studying the interplay between genetics and epigenetics influences on social behavior in male rats obtained by two different breeding schemes: a first group by breeding of knock-out (KO) male rats with wild-type (WT) female dams (homogeneous heterozygous offspring, termed MAT-HET), and a second group of heterozygous DAT male offspring by breeding of KO male and DAT-heterozygous female subjects (to obtain comparable control pups, termed MIX-HET). Their social behavior was then assessed by partner preference, social preference and elicited preference tests. In the first test MIX-HET and MAT-HET male mice had choice between two WT females one in estrous and the other not in estrous. In the second test they met either a MIX-HET or a WT male rodent. Also, the expression of the noradrenaline transporter (NET) was assessed in the prefrontal cortex, hippocampus and hypothalamus of MAT, MIX and WTs by immunofluorescence in order to estimate its involvement in the expression of social behavior. Our results show that MIX-HET focal rodents tend to have an asocial behavior when in contact with a female in estrous, and their behavior is similar to when the stimulus is a MIX-HET male. MAT-HET male rodents, instead, tend to be very attracted by the female in estrous, but they ignore the MIX-HET stimulus. MIX-HET progeny showed a lower expression of noradrenaline transporter in both hypothalamus and hippocampus with respect to MAT-HET rats, whereas MAT-HET rats displayed increased noradrenaline transporter immunofluorescence in the hypothalamus and in the hippocampus with respect to WT rats, while no difference was observed in the prefrontal cortex. Therefore we can hypothesize that the differences observed between the two heterozygous groups may be attributable to an epigenetic factor: the different maternal care received. These data can open new perspectives towards increased the preclinical knowledge about autism and bipolar disorder.

Subject Areas

dopamine transporter; socio-sexual reward; social behavior; parent-of-origin effect

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our diversity statement.

Leave a public comment
Send a private comment to the author(s)
Views 0
Downloads 0
Comments 0
Metrics 0


×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.