The effects of amfonelic acid alone and in combination with naloxone on brain-stimulation reward

Thresholds for rewarding brain stimulation delivered to the medial forebrain bundle-lateral hypothalamus were determined by means of a rate-free psychophysical method. Amfonelic acid (AFA), an indirect dopamine agonist, alone caused a significant dose-dependent lowering of the rewarding threshold. Although naloxone treatment by itself did not significantly alter the reward threshold, it blocked AFA's threshold lowering effect in every animal at one or more of the dose combinations of the two drugs tested. Naloxone was found to be more effective in blocking the threshold lowering actions of a higher (1 mg/kg) dose as opposed to a lower (0.25 mg/kg) dose of AFA. Since a lowering of threshold for rewarding intracranial stimulation is a model for drug-induced euphoria, the findings presented here indicate that AFA may have abuse potential. Furthermore, these results suggest that endogenous opioid systems may begin to modulate the effects of AFA on the reward system only when a certain level of activation of dopaminergic systems is reached.