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. 2020 Aug 12:14:142.
doi: 10.3389/fnbeh.2020.00142. eCollection 2020.

Neonatal Tactile Stimulation Alters Behaviors in Heterozygous Serotonin Transporter Male Rats: Role of the Amygdala

Karine Roversi  1 , Carolina Buizza  2 , Paola Brivio  2 , Francesca Calabrese  2 , Michel M M Verheij  3 , Caren T D Antoniazzi  4 , Marilise E Burger  1 , Marco A Riva  2 , Judith R Homberg  3
Affiliations

Neonatal Tactile Stimulation Alters Behaviors in Heterozygous Serotonin Transporter Male Rats: Role of the Amygdala

Karine Roversi et al. Front Behav Neurosci. .

Abstract

The serotonin transporter (SERT) gene, especially the short allele of the human serotonin transporter linked polymorphic region (5-HTTLPR), has been associated with the development of stress-related neuropsychiatric disorders. In line, exposure to early life stress in SERT knockout animals contributes to anxiety- and depression-like behavior. However, there is a lack of investigation of how early-life exposure to beneficial stimuli, such as tactile stimulation (TS), affects later life behavior in these animals. In this study, we investigated the effect of TS on social, anxiety, and anhedonic behavior in heterozygous SERT knockouts rats and wild-type controls and its impact on gene expression in the basolateral amygdala. Heterozygous SERT+/- rats were submitted to TS during postnatal days 8-14, for 10 min per day. In adulthood, rats were assessed for social and affective behavior. Besides, brain-derived neurotrophic factor (Bdnf) gene expression and its isoforms, components of glutamatergic and GABAergic systems as well as glucocorticoid-responsive genes were measured in the basolateral amygdala. We found that exposure to neonatal TS improved social and affective behavior in SERT+/- animals compared to naïve SERT+/- animals and was normalized to the level of naïve SERT+/+ animals. At the molecular level, we observed that TS per se affected Bdnf, the glucocorticoid-responsive genes Nr4a1, Gadd45β, the co-chaperone Fkbp5 as well as glutamatergic and GABAergic gene expression markers including the enzyme Gad67, the vesicular GABA transporter, and the vesicular glutamate transporter genes. Our results suggest that exposure of SERT+/- rats to neonatal TS can normalize their phenotype in adulthood and that TS per se alters the expression of plasticity and stress-related genes in the basolateral amygdala. These findings demonstrate the potential effect of a supportive stimulus in SERT rodents, which are more susceptible to develop psychiatric disorders.

Keywords: Bdnf; amygdala; anxiety; neonatal period; serotonin transporter knockout; tactile stimulation.

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Figures

Figure 1
Figure 1
Schematic representation of the experimental paradigm performed in heterozygous serotonin transporter knockout (SERT+/–) and wild-type (SERT+/+) male rats exposed daily to tactile stimulation (TS) from postnatal day (PND) 8–14 or a control treatment (no TS-naïve; A). Diagrams represent the location where basolateral amygdala punches were taken for molecular analyses (adapted from Paxinos and Watson brain Atlas; B).
Figure 2
Figure 2
Social interaction test. The time spent on social contact (A), social interest (B), passive behavior (C) and non-social behavior (D) of heterozygous serotonin transporter knockout (SERT+/–) and wild-type (SERT+/+) male rats daily exposed to TS from postnatal day 8–14 or a control treatment (no TS-naïve). Data are represented as mean ± SEM. *Significantly different from naïve SERT+/+ rats, #significantly different from naïve SERT+/– rats (p < 0.05).
Figure 3
Figure 3
Elevated plus maze test. The mean time of spent in open arms (%; A), the mean of entries number in open arms (%; B), time spent in closed arms (s; C) and total distance traveled (cm; D) of heterozygous serotonin transporter knockout (SERT+/–) and wild-type (SERT+/+) male rats daily exposed to TS from postnatal day 8–14 or a control treatment (no TS-naïve). Data are represented as mean ± SEM. *Significantly different from naïve SERT+/+ rats, #significantly different from naïve SERT+/– rats (p < 0.05).
Figure 4
Figure 4
Sucrose consumption test. Sucrose preference (A) and sucrose intake (B) in heterozygous serotonin transporter knockout (SERT+/–) and wild-type (SERT+/+) male rats daily exposed to TS from postnatal day 8–14 or a control treatment (no TS-naïve). Data are represented as mean ± SEM. *Significantly different from naïve SERT+/+ rats, #significantly different from naïve SERT+/–rats (p < 0.05).
Figure 5
Figure 5
Total Bdnf (A), Bdnf long 3’-UTR (B), Bdnf exon IV (C) and exon VI (D) mRNA levels in the basolateral amygdala of heterozygous serotonin transporter knockout (SERT+/–), and wild-type (SERT+/+) male rats daily exposed to TS from postnatal day 8–14 or a control treatment (no TS-naïve). Data are expressed as a percentage of naïve SERT+/+ rats (set at 100%) and are presented as mean ± SEM. *Significantly different from naïve SERT+/+ rats (p < 0.05).
Figure 6
Figure 6
Glucocorticoid receptor (Nr3c1) (A), mineralocorticoid receptor (Nr3c2) (B), and the ratio between Nr3c1 and Nr3c2 (C) mRNA levels in the basolateral amygdala of heterozygous serotonin transporter knockout (SERT+/–), and wild-type (SERT+/+) male rats daily exposed to TS from postnatal day 8–14 or a control treatment (no TS-naïve). Data are expressed as a percentage of naïve SERT naïve rats (set at 100%) and are presented as mean ± SEM. *Significantly different from naïve SERT+/+ rats, #significantly different from naïve SERT+/– rats (p < 0.05).
Figure 7
Figure 7
Nr4a1(A), Gadd45β (B) and Fkbp5 (C) mRNA levels in the basolateral amygdala of heterozygous serotonin transporter knockout (SERT+/–), and wild-type (SERT+/+) male rats daily exposed to TS from postnatal day 8–14 or a control treatment (no TS-naïve). Data are expressed as a percentage of naïve SERT+/+ rats (set at 100%) and are presented as mean ± SEM. *Significantly different from naïve SERT+/+ rats, #significantly different from naïve SERT+/– rats (p < 0.05).
Figure 8
Figure 8
Gad67 (A), Parvalbumin (Pvalb; B) and vesicular GABA transporter (Vgat; C) mRNA levels in the basolateral amygdala of heterozygous serotonin transporter knockout (SERT+/–) and wild-type (SERT+/+) male rats exposed to TS from postnatal day 8–14 or a control treatment (no TS-naïve). Data are expressed as a percentage of naïve SERT+/+ (set at 100%) and are represented as mean ± SEM. *Significantly different from naïve SERT+/+ rats (p < 0.05).
Figure 9
Figure 9
Vesicular glutamate transporter (Vglut; A) and the ratio between Vglut and vesicular GABA transporter (Vgat; B) mRNA levels in the basolateral amygdala of heterozygous serotonin transporter knockout (SERT+/–) and wild-type (SERT+/+) male rats exposed to TS from postnatal day 8–14 or a control treatment (no TS-naïve). Data are expressed as a percentage of naïve SERT+/+ (set at 100%) and are represented as mean ± SEM. *Significantly different from naïve SERT+/+ rats (p < 0.05).
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