Two distinctive apomorphine-induced phenotypes in the Roman high- and low-avoidance rats

Abstract

Strain differences in spontaneous locomotor activity and the behavioral patterns induced by dopaminergic agonists in rodents can disclose differential genetic susceptibilities to dopaminergic dysfunction (i.e. vulnerability to psychosis). Psychogenetic selection of hypoemotional Roman High-Avoidance (RHA) and hyperemotional Low-Avoidance (RLA) rats leads to divergence in dopaminergic function as well. The present study was designed to characterize their spontaneous activity and their responses to apomorphine (0.067–3 mg/kg, s.c.) as compared to those of the standard Sprague–Dawley (SD) strain. The Roman strains displayed higher spontaneous activity than SD rats and RHA exhibited the higher response to novelty which agrees with a higher sensitivity to apomorphine in this strain. The biphasic effect induced by apomorphine (locomotor inhibition and yawning at low doses but stimulation of locomotion and stereotyped behavior at higher ones) was reproduced in the standard SD strain. Low doses were less effective inducing locomotor inhibition in RHA whereas these animals were much more sensitive to high dose-induced stereotyped behavior. In contrast, RLA was characterized as a high-yawning strain and low doses of apomorphine also induced a striking motor inhibition suggesting functional enhancement of dopamine receptors mediating these behaviors. The detailed and distinctive behavioral profiles described in this work suggest between strain differences both at the presynaptic and postsynaptic dopaminergic function and may serve as paths to better specify functional mechanisms in future studies of risk of developing dopaminergic dysfunctions.