Supplementary Figure 4: Training data and additional test data for animals used to assess the effects of acute or repeated SYN119 treatment on cue-induced cocaine-seeking.

Experimental timeline (a) and self-administration (SA) training data (b, left panel; averaged over days 1-10 ± s.e.m.) for all animals shown in Fig. 2e of the main text. During these sessions, nose-poking in the active hole (AH) resulted in a cocaine infusion (0.5 mg/kg/infusion) paired with a cue-light, while nose-poking in the inactive hole (IH) was without consequence. Rats clearly learned to discriminate between the drug-paired AH and the unpaired IH. No differences were observed in average AH or IH responding or in overall drug intake (infusions obtained) between rats destined for acute vehicle or acute SYN treatment groups. Right panel of b: Data shown are the mean (± s.e.m.) number of responses in the IH during two tests for cue-induced cocaine seeking. The first test was performed on withdrawal day (WD) 1. The second test was performed on WD45 or greater, 20 min after acute injection of SYN. No group differences were observed on either test day, indicating that acute SYN injection did not affect IH responding. Thus, its effects were specific to AH responding (shown in Fig. 2e of the main text). (c,d) Experimental timeline (c) and SA training data (d, left panel) for rats destined for the repeated vehicle or repeated SYN treatment groups shown in Fig. 5 of the main text (details same as described above for panel b). No differences were observed between rats destined for the two treatment groups. Right panel: Data shown are mean (± s.e.m.) number of responses in the IH during two tests for cue-induced cocaine seeking. The first test was performed on WD1. The second test was performed 0-5 days after discontinuing repeated SYN injections. No group differences were observed on either test day, indicating that repeated SYN injections did not affect IH responding. Thus, effects of this treatment are specific to AH responding (shown in Fig. 5a,b of the main text).