Activation of alpha 2-adrenoceptors suppresses excessive wheel running in the semistarvation-induced hyperactive rat.

Male Wistar rats were housed in cages linked to running wheels and fed on a schedule designed to reduce their body weight by 20-30%. During this period of semistarvation, rats increased their daily running wheel activity (RWA) by up to 30 km/day. RWA could be kept at this level provided that body weight was kept constant. Different alpha-adrenergic agonists and antagonists were tested for their effects on RWA and it was found that RWA could be suppressed only by agonists that display high affinity for the alpha 2-receptor (clonidine and guanfacine). Neither antagonist had an effect on RWA. Clonidine's inhibiting effect on RWA was prevented by pretreatment with yohimbine, which also has high affinity for alpha 2-receptors. From these results, we conclude that semistarvation-induced hyperactivity can be blocked by alpha 2-agonists. In view of this result and those that were obtained in previous studies, a theoretical model for the development of semistarvation-induced hyperactivity will be presented.