Dysfunction of the central dopamine D 2 -receptor-related network has been proposed to play a critical role in dopamine-related diseases, such as schizophrenia and drug dependence. Generally, the stimulation of dopamine D 2 -receptors on medium spiny neurons (MSN) induces several behavioral effects, such as sedation, hallucination, aversion and motivation. Furthermore, such physiological responses through dopamine D 2 -receptor-containing MSN (D 2 -MSN) may be synchronized with the activity of dopamine D 1 -receptor-containing MSN (D 1 -MSN), or both may exhibit dual agonistic/antagonistic innervation. In the present study, we characterized the discriminative stimulus effect of the selective dopamine D 2 -receptor agonist quinpirole to further investigate the "D 1/ D 2 -MSN" interaction using dopamine-related agents, hallucinogens and sedatives in rats. Among dopamine receptor agonists, only selective dopamine D 2 -receptor agonists substituted for the discriminative stimulus effects of quinpirole. Neither the δ-opioid receptor agonist SNC80 nor the adenosine A 2A -receptor antagonist istradefylline, both of which may act on D 2 -MSNs, substituted for the discriminative stimulus effects of quinpirole. Interestingly, the dopamine D 1 -receptor antagonist SCH23390 and the GABA B -receptor agonist baclofen, but not hallucinogens or sedatives, substituted for the discriminative stimulus effects of quinpirole. These results suggest that stimulation of central dopamine D 2 -receptors exerts a distinct discriminative stimulus effect, and blockade of dopamine D 1 -receptors and agonistic modulation of GABA B -receptors may share the discriminative stimulus effect via the activation of central dopamine D 2 -receptors. • The specific stimulation of central dopamine D 2 -receptors contributes to the discriminative stimulus effects of quinpirole. • Antagonism of dopamine D 1 -receptors share the discriminative stimulus effects of the D 2 -receptor agonist quinpirole. [ABSTRACT FROM AUTHOR]