Effects of dopamine D4 receptor antagonist on spontaneous alternation in rats

The present study was a component of a series of studies scrutinising the neuroreceptor substrate of behavioural flexibility in a rat model. Spontaneous alternation paradigms model the natural tendency of rodents to spontaneously and flexibly shift between alternative spatial responses. In the study it was tested for the first time if the neurochemical substrate mediating spontaneous alternation behaviour includes the dopamine D4 receptor.

The acute effects of the highly selective dopamine D4 receptor antagonist L-745,870 on rats' performance in a spontaneous alternation paradigm in a T-maze were examined. The paradigm was a food-rewarded continuous trial procedure performed for 20 trials.

The spontaneous alternation rate was not affected by the doses of the drug administered (0.02 mg/kg; 0.2 mg/kg; 2 mg/kg), but the position bias of the group receiving the highest L-745,870 dose (2 mg/kg) was significantly increased compared to the group that received the lowest dose (0.02 mg/kg). No significant effects on position bias were found compared to saline. The drug did not increase response perseveration.

The results show that the neural substrate mediating the spatial distribution of responses in the spontaneous alternation paradigm includes the D4 receptor. However, the statistically significant effect of L-745,870 on position bias was found comparing a high drug dose with a low drug dose, and not comparing the drug doses with saline. For the tested doses of L-745,870 the effect on position bias was not large enough to affect the alternation rate.