Contingency learning in zebrafish exposed to apomorphine- and levetiracetam

Christoffel van der Westhuizen, Tarryn L. Botha, Karin Finger-Baier, Geoffrey de Brouwer, De Wet Wolmarans

Research output: Contribution to journalArticlepeer-review


Cognitive rigidity (CR) refers to inadequate executive adaptation in the face of changing circumstances. Increased CR is associated with a number of psychiatric disorders, for example, obsessive-compulsive disorder, and improving cognitive functioning by targeting CR in these conditions, may be fruitful. Levetiracetam (LEV), clinically used to treat epilepsy, may have pro-cognitive effects by restoring balance to neuronal signalling. To explore this possibility, we applied apomorphine (APO) exposure in an attempt to induce rigid cue-directed responses following a cue (visual pattern)-reward (social conspecifics) contingency learning phase and to assess the effects of LEV on such behaviours. Briefly, zebrafish were divided into four different 39-day-long exposure groups (n = 9–10) as follows: control (CTRL), APO (100 µg/L), LEV (750 µg/L) and APO + LEV (100 µg/L + 750 µg/L). The main findings of this experiment were that 1) all four exposure groups performed similarly with respect to reward- and cue-directed learning over the first two study phases, 2) compared to the CTRL group, all drug interventions, but notably the APO + LEV combination, lowered the degree of reward-directed behaviour during a dissociated presentation of the cue and reward, and 3) temporal and spatial factors influenced the manner in which zebrafish responded to the presentation of the reward. Future studies are needed to explore the relevance of these findings for our understanding of the potential cognitive effects of LEV.

Original languageEnglish
Pages (from-to)424-436
Number of pages13
JournalBehavioural Pharmacology
Issue number7
Publication statusPublished - 1 Oct 2023


  • Danio rerio
  • apomorphine
  • cognitive flexibility
  • cognitive rigidity
  • goal-directed behaviour
  • levetiracetam
  • zebrafish

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental Health


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