Effects of specific dopamine D1 and D2 receptor antagonists and agonists and neuroleptic drugs on emotional defecation in a rat model of akathisia.

An increase in emotional defecation in rats in a well-habituated environment induced by neuroleptic drugs (NDef) has been proposed as a model for neuroleptic-induced akathisia. We examined the effects of dopamine receptor antagonists and agonists on this model. A selective dopamine D1 antagonist (SCH 23390) and a selective D2 antagonist (raclopride) induced increased defecation at higher doses, and demonstrated a synergistic effect at lower doses. Selective D1 (SKF 82958) and D2 (quinpirole) agonists did not have a significant effect on defecation, nor did they reverse the effect of haloperidol. In a further pilot study, we explored the effects of typical and atypical neuroleptics on this model. The haloperidol and risperidone treated rats produced more faecal boli than those treated with clozapine, thioridazine and chlorpromazine, with the former being non-significantly greater than the vehicle-treated group. The results of our studies suggest that NDef is most probably an effect of central dopamine antagonism that is not specific to D1 or D2 receptors, but that the two receptor subtypes have a synergistic effect. It is unlikely to be due to actions of neuroleptics on 5HT2 or alpha1 receptors as has sometimes been suggested. The results have implications for our understanding of the pathogenesis of akathisia.