Novelty response of rats determines the effect of prefrontal alpha-2 adrenoceptor modulation on anxiety

In this study we provide evidence that animals of the same population, although identical in age and sex, have individual reactions to the prefrontal modulation of adrenoceptors. We have examined the dose-dependent action of α2-adrenoceptor agents on the anxiety of rats with different response to novelty in the elevated plus maze (EPM) apparatus. Rats were divided into high (HR) and low responder (LR) groups based on their locomotor activity in a novel open field environment. HR rats also showed increased locomotion and low anxiety in the EPM. Prefrontal injection of α2-receptor antagonist yohimbine, BRL44408 or imiloxan caused anxiety only in HR rats. The α2A/D-receptor agonist guanfacine increased anxiety levels of both groups. However, the effective dose was lower in HR rats. The present results propose different prefrontal adrenoceptor sensitivity of rats showing distinct baseline activity levels.

► High and low novelty responder (HR/LR) rats show distinct baseline anxiety levels.
► Cortical α2 adrenergic receptor mechanisms modulate anxiety of HR and LR rats.
► Prefrontally applied yohimbine, BRL44408 or imiloxan elicit anxiety only in HR rats.
► Guanfacine increases anxiety of both groups, with lower effective doses in HR rats.
► Results propose different prefrontal adrenoceptor sensitivity of HR and LR rat groups.