Indicating that ACD-seeking behaviour directly depends on DA neurotransmission. In order to assess the role of dopamine neurotransmission on the reinstatement of ACD consumption following a period of forced abstinence, quinpirole was administered during relapse. In particular, along the relapse experiment, animals were administered with quinpirole during day 2, 3 and 4, in order to consider day 1 as a reference of the baseline drinking behaviour, and to evaluate drinking behaviour restoration, once the administration ceased at day 5. Quinpirole was able to decrease the number of responses emitted and, induced a significant reduction in ACD intake, within the quinpirole treated group, when compared with the first and the last relapse days. Accordingly, the dose of quinpirole used in these experiments has previously been shown to decrease ethanolreinforced responding, likely by disrupting dopamine transmission, via pre-synaptic receptors stimulation. It has long been known that activation of D2-like receptors hyperpolarizes DA neurons and inhibits their firing activity. Consistent with these data, anatomical studies revealed that D2-like receptors are predominantly expressed on the dendrites of DA neurons, where their inhibitory activity plays a predominant role. Quinpirole, activating D2 pre-synapting autoreceptors, appears to dissociate the process of primary reinforcement from processes regulating instrumental response initiation, maintenance, and selection, hence leading to a decrease in ACDattributed salience, and consequently in the motivation to work for drug self-administration. In agreement with previous studies and consistently with the pre-synaptic action exerted, quinpirole reduced locomotor activity in terms of total distance travelled, when tested in the Open Field. Nevertheless, no differences in rats’ behavioural reactivity in the operant chamber were observed during the operant self-administration sessions, ruling out a non-specific effect of the drug in the reduction of the operant behaviour. Indeed, when tested on the operant-drinking behaviour for water, quinpirole did not exert any effect, with respect to vehicle, highlighting a specific activity on motivation for ACD. A different activity on the DAergic synapse, i.e. a post-synaptic receptor modulation, was achieved by ropinirole administration. Ropinirole is a well-tolerated, selective D2-D3 agonist used in improving the motor symptoms of Parkinson’s Disease, hence able to increase DA neurotransmission. Due to its post junctional activity, ropinirole was administered during extinction in order to verify whether it was able to affect drug-seeking behaviour. Our results show that ropinirole failed to induce any modification in lever pressing. This result is consistent with ropinirole activity in promoting dopamine signalling, but since ropinirole is devoid of abuse liability.