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. Author manuscript; available in PMC: 2024 Sep 11.
Published in final edited form as: Biol Psychiatry. 2020 Feb 29;88(12):898–909. doi: 10.1016/j.biopsych.2020.02.019

Figure 4. Systemic pharmacological manipulation of the M4 muscarinic acetylcholine receptor in alcohol consumption and seeking.

Figure 4.

To functionally test the role of M4 mAChRs in alcohol consumption and seeking we systemically administered a selective M4 positive allosteric modulator, VU0467154, as outlined in (A). Systemic administration of VU0467154 (30 mg/kg, p.o) significantly reduced (B) active lever responding (n=8) in FR3 self-administration (treatment x lever interaction, F(1,7) = 17.09, p = 0.004; Bonferroni post hoc analysis, vehicle vs. VU0467154, p = 0.0015), (C) Breakpoint (n=10) in the progressive ratio paradigm (t = 2.47, df = 9, p = 0.035), (D) active lever responding (n=8) in cue-induced reinstatement of alcohol seeking (treatment x lever interaction, F(2.12) = 13.91, p = 0.0007; Bonferroni post hoc, extinction vs. vehicle, p = 0.0001, vehicle vs VU0467154, p = 0.0013). No effect was observed on natural reward consumption during (E) active lever responding (n=8) in sucrose self-administration (F(1,14) = 0.418, p = 0.529), or (F) ataxia (n=13) determined via performance on the rotarod (t = 0.234, df = 11, p = 0.819). Data expressed as mean ± SEM, *p < 0.05, **p < 0.01, ***p < 0.001.