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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 5. Dorsolateral striatum pharmacological manipulation of the M4 muscarinic acetylcholine receptor in alcohol consumption and seeking.

Figure 5.

To determine the role of dorsolateral (DLS) M4 mAChRs in alcohol consumption and seeking we microinjected the selective M4 mAChR PAM, VU0467154, into the DLS prior to self-administration (n=12) and cue-induced reinstatement (n=7) as outlined in (A). Intra-DLS VU0467154 (3 μmol/hemisphere) reduced (B) active lever responding in alcohol self-administration (treatment x lever interaction F(1,11) = 5.67, p = 0.0364; Bonferroni post hoc, active lever vehicle vs VU0467154, p = 0.0086). This reduction occurred during peak responding (treatment x time interaction F(3,33) = 8.52, p = 0.0002. Bonferroni post hoc analysis, vehicle vs VU0467154 at 5 min, p <0.0001). (C) Intra-DLS VU0467154 (3 μmol/hemisphere) also reduced active lever responding during cue-induced reinstatement of alcohol seeking (treatment x lever, F(2,12) = 11.22, p = 0.0018; Bonferroni post hoc, extinction vs. vehicle, p = 0.0004, vehicle vs. VU0467154, p = 0.0016). Decreased lever pressing was significantly reduced during peak responding (treatment x time interaction F(3,18) = 3.729, p = 0.0303. Bonferroni post hoc analysis, treatment vs. vehicle at 5 min, p = 0.0067). (D) Shows the injection sites for VU0467154 in self-administration (light blue) and cue-induced reinstatement (dark blue)(36). Data are expressed as mean ± SEM, **p < 0.01, ****p < 0.0001.