In the central nervous system when administered i.p. at doses of 100 mg/kg. According to our data, ACD intake reached mean values of 665,3 mg/kg, within the 20 min-operant session, and it is conceivable that such chronic and increasing intake of ACD can overwhelm the metabolic barrier constituted by epithelial aldehyde dehydrogenase, a low Km ACD-oxidizing enzyme expressed in gastrointestinal tract. Systemic absorption after ACD oral ingestion has been already demonstrated by previous studies on ACD self-administration by Peana and colleagues. Therefore, increasing blood ACD concentrations could saturate the moderate aldehyde dehydrogenase activity of BBB capillaries, enter the brain, and exert central activity. Our results are in agreement with previous data from this laboratory, and can be ascribed to the rewarding and motivational properties of ACD. Animals easily self-administer ACD, likely as a consequence of its reinforcing properties, reported to be 1000-fold stronger than ethanol’s. Although apparently in opposition with reports on primarily ACD aversive effects following acute peripheral administration, our results must be interpreted in the context of the particular experimental protocol. ACD operant-drinking behaviour is induced and maintained along a relatively long period, which is likely required for exerting pharmacologically significant central effects. On the other hand, our findings are in line with early studies reporting positive euphoric effects following moderate consumption of ethanol in subjects treated with aldehyde dehydrogenase inhibitors, such as disulfiram. DA involvement in the operant behaviour for ACD was assessed by using quinpirole and ropinirole, DA D2 receptor-selective ligands with a different pharmacodynamic profile, whose administration aimed at selectively modulate the DAergic synapse in different functional states. Indeed, the rationale of the experiment was that quinpirole, administered during extinction and relapse, could phasically inhibit DAergic signalling, as a consequence of its activity as agonist at D2 receptors in the presynaptic terminal, and reduce thus drug-seeking behaviour; ropinirole, on the other hand, as a D2-D3 receptor agonist, was administered daily during the deprivation period in order to stimulate the DAergic post-synaptic terminal, thus reducing the craving for the substance during reinstatement. Our data clearly show that, when tested during extinction, quinpirole acute administration was able to decrease the number of lever presses, when compared with vehicle. Lever pressing is thought to reflect learned processes related to motivation to seek the substance and it is to be considered as a measure of appetitive “ACD seeking-like” behaviour, which is in turn related to the induction of mesolimbic DA release. Our evidence shows that quinpirole, at the doses used in this study, is responsible for the decrease in the number of lever presses.