Effects of serta and sertb knockout on aggression in zebrafish (Danio rerio).

Zebrafish (Danio rerio) are unusual in having two paralogues of the serotonin re-uptake transporter (Sert), slc6a4a (serta) and slc6a4b (sertb), the transporter that serves in serotonin re-uptake from a synapse into the pre-synaptic cell or in serotonin uptake from the extracellular milieu into cells in the peripheral tissues. To address a knowledge gap concerning the specific roles of these paralogues, we used CRISPR/Cas9 technology to generate zebrafish knockout lines predicted to lack functional expression of Serta or Sertb. The consequences of loss-of-function of Serta or Sertb were assessed at the gene expression level, focusing on the serotonergic signalling pathway, and at the behaviour level, focusing on aggression. Whereas serta mRNA was expressed in all tissues examined, with high expression in the heart, gill and brain, only the brain displayed substantial sertb mRNA expression. In both serta-/- and sertb-/- fish, changes in transcript abundances of multiple components of the serotonin signalling pathway were detected, including proteins involved in serotonin synthesis (tph1a, tph1b, tph2, ddc), packaging (vmat2) and degradation (mao), and serotonin receptors (htr1aa, htr1ab). Using a mirror aggression test, serta-/- male but not female fish exhibited greater aggression than wildtype fish. However, both male and female sertb-/- fish displayed less aggression than their wildtype counterparts. These differences in behaviour between serta-/- and sertb-/- individuals hold promise for increasing our understanding of the neurophysiological basis of aggression in zebrafish.

Spiroperidol, but not eticlopride or aripiprazole, produces gradual increases in descent latencies in the bar test in rats.

Rats repeatedly exposed to the bar test following injections with a dopamine D2-like receptor antagonist such as haloperidol show increased descent latencies, suggesting that contextual stimuli may lose their ability to elicit approach and other responses. Here, we showed that rats took progressively longer to initiate descent from a horizontal bar across sessions following daily intraperitoneal treatment (paired group) with the D2-like receptor antagonist, spiroperidol (0.125 and 0.25 mg/kg), but not in the control group that received 0.25 mg/kg in their home cage and testing following saline. When both groups were tested following an injection of spiroperidol or following saline, a sensitized and a conditioned increase in descent latency, respectively, were observed in the paired but not in the unpaired group. No evidence of sensitization or conditioning was found with the substituted benzamide compound, eticlopride (0.15-0.5 mg/kg), or the D2-like receptor partial agonist, aripiprazole (0.25-0.5 mg/kg). The different effects of these agents on learning may be related to different region-specific affinities for dopamine receptors or differences in receptor dissociation profiles. We suggest that the behavioural changes observed in spiroperidol-treated rats may reflect inverse incentive learning.