Developmental social isolation affects adult behavior, social interaction, and dopamine metabolite levels in zebrafish

Abstract

The zebrafish is a social vertebrate and an excellent translational model for a variety of human disorders. Abnormal social behavior is a hallmark of several human brain disorders. Social behavioral problems can arise as a result of adverse early social environment. Little is known about the effects of early social isolation in adult zebrafish. We compared zebrafish that were isolated for either short (7 days) or long duration (180 days) to socially housed zebrafish, testing their behavior across ontogenesis (ages 10, 30, 60, 90, 120, 180 days), and shoal cohesion and wholebrain monoamines and their metabolites in adulthood. Long social isolation increased locomotion and decreased shoal cohesion and anxiety in the open-field in adult. Additionally, both short and long social isolation reduced dopamine metabolite levels in response to social stimuli. Thus, early social isolation has lasting effects in zebrafish, and may be employed to generate zebrafish models of human neuropsychiatric conditions. K E Y W O R D Sanxiety, dopamine, locomotor activity, social behavior, social isolation, Zebrafish

Conserved serotonergic background of experience-dependent challenge-responding in zebrafish (Danio rerio)

“…Our findings regarding brain 5-HT levels are in contradiction with previous reports, however, this discrepancy might be explained by the facts that in these papers either i.) only extracellular 5-HT content was measured and ii) adult animals were employed (Maximino et al, 2013b) or iii) social isolation was conducted in adult fish or in larvae from the age of 0 dpf (Shams et al, 2017a, 2017b, 2015). The latter case, together with rodent data supports that the period during which isolation occurs is fundamental regarding later consequences, highlighting the importance of critical and sensitive developmental periods (Einon and Morgan, 1977; Fone and Porkess, 2008; Hall, 1998; Lukkes et al, 2009a).…”

“…One can hypothesize that a low stress-induced cortisol response, without any change in basal levels, and the accompanying low avoidance behavior might indicate a malfunction of challenge-responding. This phenotypic background may account for low avoidance in adult and decreased locomotion in 30 dpf juvenile zebrafish after social isolation as well, observed by Shams and colleagues (Shams et al, 2017a, 2015). This theory is also supported by our findings on isolation-induced low, delayed avoidance and inadequate arousal in response to a challenge and enhanced arousal under baseline, resting conditions.…”

The lonely fish is not a loner fish: whole-brain mapping reveals abnormal activity in socially isolated zebrafish

“…In contrast, anti-social, C (-S), fish showed a large decrease in activation in an adjacent, non-overlapping area of the ventral caudal hypothalamus ( Figure 2B and 2D, C (-S) vs C (nsc) p=0.003, Mann-Whitney test). This functional division in the hypothalamus seems to mirror the distribution of dopaminergic and serotoninergic markers (Filippi, Mahler, Schweitzer, & Driever, 2010;Lillesaar, 2011) (Figure 2C), suggesting that this area could be responsible for the changes of serotonin and dopamine levels widely reported in fish viewing social cues (Huang et al, 2015;Soaleha Shams, Amlani, Buske, Chatterjee, & Gerlai, 2018). In the preoptic area, we observed only a small dorsal (PM) increase and ventrolateral (Pa) decrease in activity, which was significant only in the Pa of anti-social control fish (C(-S) vs C (nsc) p=0.003 Mann-Whitney, Figure 2B and 2D).…”

Early-life social experience shapes social avoidance reactions in larval zebrafish

“…Social experiences during early development can have long lasting effects on social and other behaviors, as shown by the devastating phenotype of rhesus monkeys raised with social deprivation described by Harlow et al [1965]. Since then, numerous studies have reported effects of social isolation raising in a variety of species, including rodents [Heidbreder et al, 2000, Lukkes et al, 2009], cockroaches [Lihoreau et al, 2009], lizards [Ballen et al, 2014], mites [Schausberger et al, 2017] and fish [Hesse et al, 2015, Shams et al, 2018]. Yet, the underlying mechanisms of how social experiences shape behavior and brain development have yet to be fully understood.…”