Small rodents (mice, rats) are the species of choice for evaluating the pharmacology of centrally acting compounds, such as
antipsychotics, whereas toxicology data are routinely obtained from other species (rabbits, dogs, monkeys). Whilst there is a substantial number of "therapeutically relevant" pharmacological models for "
antipsychotic-like" activity in small rodents, based on hyperdopaminergic or hypoglutamatergic/
NMDA approaches, there is a remarkable paucity of such models in other species. Here, we compared the efficacy and potency of reference and new generation
dopamine D2/5-HT(1A) putative
antipsychotics, administered orally, against
apomorphine-induced
emesis in dogs, a model of central D2 receptor activation that can be implemented with relative ease.
Risperidone potently and fully (10 microg/kg) prevented
emesis/retching induced by 0.1 mg/kg s.c.
apomorphine.
SLV313 and
F15063 (D2 receptor
antagonists/5-HT(1A) receptor agonists) also abolished
emesis/retching, albeit less potently than
risperidone (minimal effective dose, MEDs: 10 and 40 microg/kg, respectively). The D2 receptor partial agonists/5-HT(1A) receptor agonists
aripiprazole and
bifeprunox, (up to 80 microg/kg) only partially attenuated
emesis, as did the peripheral D2 receptor antagonist
domperidone. Under the present experimental conditions,
haloperidol was only efficacious at the highest dose tested (320 microg/kg). To summarize, dogs are very sensitive to the dopaminergic blocking effects of
antipsychotics in this model of D2 receptor activation. This model can thus be advantageously used to investigate the pharmacological activity of novel D2 receptor antagonists/partial agonists in dogs.