Dopaminergic and serotonergic modulation of social reward appraisal in zebrafish (Danio rerio) under circumstances of motivational conflict: Towards a screening test for anti-compulsive drug action.

Cognitive flexibility, shown to be impaired in patients presenting with compulsions, is dependent on balanced dopaminergic and serotonergic interaction. Towards the development of a zebrafish (Danio rerio) screening test for anti-compulsive drug action, we manipulated social reward appraisal under different contexts by means of dopaminergic (apomorphine) and serotonergic (escitalopram) intervention. Seven groups of zebrafish (n = 6 per group) were exposed for 24 days (1 h per day) to either control (normal tank water), apomorphine (50 or 100 µg/L), escitalopram (500 or 1000 µg/L) or a combination (A100/E500 or A100/E1000 µg/L). Contextual reward appraisal was assessed over three phases i.e. Phase 1 (contingency association), Phase 2 (dissociative testing), and Phase 3 (re-associative testing). We demonstrate that 1) sight of social conspecifics is an inadequate motivational reinforcer under circumstances of motivational conflict, 2) dopaminergic and serotonergic intervention lessens the importance of an aversive stimulus, increasing the motivational valence of social reward, 3) while serotoninergic intervention maintains reward directed behavior, high-dose dopaminergic intervention bolsters cue-directed responses and 4) high-dose escitalopram reversed apomorphine-induced behavioral inflexibility. The results reported here are supportive of current dopamine-serotonin opponency theories and confirm the zebrafish as a potentially useful species in which to investigate compulsive-like behaviors.

Retinal ganglion cell genesis requires lakritz, a Zebrafish atonal Homolog.

Mutation of the zebrafish lakritz (lak) locus completely eliminates the earliest-born retinal cells, the ganglion cells (RGCs). Instead, excess amacrine, bipolar, and Müller glial cells are generated in the mutant. The extra amacrines are found at ectopic locations in the ganglion cell layer. Cone photoreceptors appear unaffected by the mutation. Molecular analysis reveals that lak encodes Ath5, the zebrafish eye-specific ortholog of the Drosophila basic helix-loop-helix transcription factor Atonal. A combined birth-dating and cell marker analysis demonstrates that lak/ath5 is essential for RGC determination during the first wave of neurogenesis in the retina. Our results suggest that this wave is skipped in the mutant, leading to an accumulation of progenitors for inner nuclear layer cells.