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. 2023 Sep 28;28(11):4666–4678. doi: 10.1038/s41380-023-02256-z

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© The Author(s) 2023

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 4 — Intra-anterior dorsolateral striatum (aDLS) infusion of the dopamine receptor antagonist α-flupentixol (0, 6, 12 μg/side) had no effect on recently acquired polydipsic water drinking (Test 1, A) or on drinking shown by low drinker (LD) rats even after 20 sessions (Test 2, B). In contrast, similar intra aDLS infusions of α-flupentixol (0, 6, 12 μg/side) decreased excessive water intake in high drinkers (HD) rats (Test 2, B). When water was replaced by alcohol, intra aDLS dopamine receptor blockage no longer influenced polydipsic drinking in HD rats while it remained ineffective in LD rats (Test 3, C). In marked contrast, the sensitivity shown by HD rats to intra aDLS dopamine receptor blockade when engaged in excessive polydipsic water intake re-emerged when their polydipsic alcohol intake became well established (Test 4, D). E–H The functional engagement of the aDLS DA-dependent habit system when polydipsic water or alcohol drinking becomes compulsive, namely at tests 2 and 4, is not due to a floor effect inherent to relatively lower levels of non-prandial drinking at tests 1 and 2 since no correlations were observed between the magnitude of the decrease in fluid intake following intra aDLS infusion of either dose of α-flupentixol and the baseline level of water (E, F) or alcohol (G, H) adjunctive drinking. ** p < 0.01, * p < 0.05 different from vehicle (0 μg/side). SIPw: SIP with water; SIPa: SIP with alcohol; α-flu: α-flupentixol. ∆water intake (%bsl/veh): difference in water intake following aDLS DA receptor blockage and baseline (bsl, for test 1) or intra aDLS infusion of vehicle (for test 2). ∆alcohol intake (%bsl): difference in alcohol intake following aDLS DA receptor blockage vs intra aDLS infusion of vehicle (tests 3 and 4). In E, F pink arrows indicate the spread of the reliance on the aDLS DA-dependent system.