Go 6983 Elevation of plasma glucocorticoids as well as a
Elevation of plasma glucocorticoids as well as a sympathetic activation are highly adaptive mechanisms allowing the individual to cope in various situations . Novelty-induced increase in locomotor activity, characterizing the bold fish herein, accompanied by elevated glucocorticoids is a well-established indicative of dopamine release in the nucleus accumbens. Notably, activation of dopamine D2 receptors within the nucleus accumbens shell appear to be important for the expression of an active stress response . However, the difference in dopamine D2 receptor expression observed in the current study are not easily explained due to the complexity of the dopamine system. Most studies on dopamine function have been performed on mammals, and the fact that teleost and mammalian dopamine transmission differs (ref in ) further complicates the interpretation. However, a recent study found lower baseline dopaminergic activity in the dorsomedial telencephalon, a region with homologous functions to amygdala in mammals, in isolated rainbow trout with a phenotype resembling proactive stress coping styles . Moreover, differences in brain dopamine D2 receptor expression between dominant and subordinate zebrafish males have been reported . In their study, they found that following one day of social interaction dominant males displayed a higher hypothalamic expression of drd2c than males losing fights and becoming subordinate. The dominants also showed higher expression of hypothalamic tyrosine hydroxylase whereas drd3 expression was elevated in the telencephalon of subordinate males . In juvenile salmonids, fights for social dominance results in activation of the dopaminergic system , and dominant fish in established hierarchies show higher telencephalic levels of the dopamine metabolite homovanillic Go 6983 . However, Dahlbom et al.  did not find differences in dopamine, or dopamine metabolite concentrations, between dominant and subordinate zebrafish following five days of social interaction in pairs . The endogenous opioid system is important for many basal functions such as motivation, reproductive behavior, food and fluid intake, but also in analgesia, stress reactivity, learning and memory, reward and reinforcement, motor function, and endocrine regulation [27,, , ]. Opioid receptors are widely distributed in the central nervous system of mammals [47,48]. The endogenous opioid system has been characterized in zebrafish [16,49], but the functional role of this system is far less studied in zebrafish than in rodents. However, due to the shared evolutionary history across vertebrates  is it reasonable to assume that the opioid system has a similar function in zebrafish as in rodents and humans. The opioid receptors mu, delta and kappa, that have been identified in mammals [47,50], have also been reported in zebrafish but with two copies of the gene for the delta opioid receptor, named oprd1a and oprd1b, as a result of the teleost tetraploidization . The present results revealed higher expression of delta opioid receptors (oprd1b) in bold relative to shy fish. To the best of our knowledge, this study is the first to relate opioid receptor gene expression to behavior in zebrafish. The delta opioid receptor has been implicated in mood and emotional responses , and previous research has shown that genetic deletion of the delta opioid receptor in mice is associated with anxiety-like behavior [52,53]. Bottom-dwelling behavior, low levels of exploration and low activity in the novel tank diving test, often used for interpretation about anxiety-like behavior in zebrafish [7,19], was a characteristic of the shy fish that also displayed lower expression of delta opioid receptors (oprd1b). Moreover, rats exposed to early life adverse experiences express increased exploration and risk-taking behavior in adulthood , accompanied by low immunoreactive levels of Met-enkephalin-Arg6-Phe7, a marker of proenkephalin [55,56], and increased expression of oprd1 , which is in line with the findings herein of bold fish having higher expression of delta opioid receptors.