Article Figures & Data
Figures
- Figure 1.
Task schematic of cued and uncued rGT procedure. The rGT began with illumination of the tray light. A nose-poke response in the food tray extinguished the tray light and initiated a new trial. After an ITI of 5 s, 4 stimulus lights were turned on in holes 1, 2, 4, and 5, each of which was associated with a different number of sugar pellets (P1–P4). The animal was required to respond in one of these holes within 10 s. This response was then rewarded or punished depending on the reinforcement schedule for that option (indicated by the probability of a win or loss in brackets). If the animal was rewarded in the uncued task, then the stimulus lights were simply extinguished and the animal received the corresponding number of pellets in the now-illuminated food tray. In the cued task, reward delivery was also accompanied by audiovisual cues that increased in complexity with reward magnitude (see Table 1 for details). The duration of the cues was held constant at 2 s across all options. In both task variants, a response at the food tray then started a new trial. If the animal was punished, then the stimulus light in the corresponding hole flashed at a frequency of 0.5 Hz for the duration of the punishing time-out and all other lights were extinguished. At the end of the punishment period, the tray light was turned on and the animal could initiate a new trial. Failure to respond at the illuminated holes resulted in an omission, whereas a response during the ITI was classified as a premature response and punished by a 5 s time-out during which the house light was turned on. The order of the options from left to right is counterbalanced within each cohort (version A as shown, version B: 4, 1, 3, 2) The maximum number of pellets that could be theoretically obtained if the option was chosen exclusively in a 30 min session (not allowing time for choice/food consumption for consistency) is given, providing an objective value for each option.
- Figure 2.
A, Risky choice is higher at baseline on the cued versus uncued rGT. B, No significant preference for any option was observed on the CPT. Data shown are mean ± SEM. *p < 0.05.
- Figure 3.
Amphetamine significantly affects choice on the uncued, but not the cued, rGT. Higher doses of amphetamine significantly increased choice of P1 and decreased choice of P2 in the uncued rGT (A), but these effects did not reach statistical significance in the cued rGT (B). Data are graphed as the mean change from vehicle ± SEM to illustrate the effect of each drug across task independent of the difference in preference for each option between task variants and individual subjects. *p < 0.05.
- Figure 4.
Selective modulation of choice on the cued rGT by D3 receptor ligands. The D3 agonist PD128907 significantly increased P3 in the cued group (B), but not in the uncued group (A). SB277011-A likewise selectively affected the cued group alone and had the opposite pattern of effects to the agonist, decreasing choice of P3 (E). SB-277011-A did not affect choice in the uncued group (D). Neither PD128907 nor SB-277011-A affected choice in the cue preference group (C, F). Data are graphed as the mean change from vehicle ± SEM to illustrate the effect of each drug across task independent of the difference in preference for each option between task variants and individual subjects.
Tables
Option Cue duration Auditory cues Visual cues Variable? P1 2s 1 tone Flash H1, 2.5 Hz, 2 s No P2 2s 2 tones, in sequence 1 s each Flash H4, 2.5 Hz, 2 s No P3 2s 3 tones, in sequence 0.2 s each Flash H5, 5 Hz, 1 s; Flash H2, H3, H4, 5Hz, 1s Yes; 2 patterns P4 2s 6 tones, in sequence 0.2 s each Flash H2, 5Hz, 1s; Flash H1, H2, H3, H4, H5, 5Hz, 1s Yes; 4 patterns Drug Drug type Dose (mg/kg) Amphetamine Nonselective dopamine agonist Vehicle, 0.3, 1.0, 1.5 Eticlopride Dopamine D2 family antagonist Vehicle, 0.01, 0.03, 0.06 PD128907 Dopamine D3 agonist Vehicle, 0.01, 0.03, 0.1 SB-277011-A Dopamine D3 antagonist Vehicle, 0.5, 1.5, 5.0 PD-168077 Dopamine D4 agonist Vehicle, 0.5, 1.0, 5.0 A-391383 Dopamine D4 antagonist Vehicle, 0.5, 1.0, 5.0 - Table 3.
All behavioral variables at baseline and after D3 ligand administration in the uncued rGT, cued rGT, and CPT
Trials Prematures (%) Choice latency (s) Collection latency (s) Omissions (%) Uncued rGT 99.87 ± 8.28 21.05 ± 3.61 1.30 ± 0.23 1.36 ± 0.32 0.76 ± 0.31 Cued rGT 79.69 ± 7.40 23.87 ± 3.83 1.24 ± 0.17 0.84 ± 0.09 1.40 ± 0.86 CPT 101.04 ± 9.75 10.79 ± 0.67 2.05 ± 0.18 2.30 ± 0.11 4.58 ± 0.78 Baseline data broadly resembled that published previously (see recent meta-analysis by Barrus et al., 2015. Premature responding correlated with risky choice in this dataset (r(31) = 0.38, p = 0.035), although, as we have discussed before (Barrus et al., 2015), we do not believe that this relationship is causative. Although animals appeared to more quickly choose the more risky options (data not shown), this difference was not statistically significant (choice; F(3,36) = 1.82, p = 0.161) and there was no relationship between choice preference and choice latency (r = −0.001, p = 0.995). Data shown are group mean ± SEM.
- Table 4.
Percent choice of each option after amphetamine (amph), PD128907 (PD), or SB-277011-A (SB)
Dose (mg/kg) Uncued rGT (% choice) Cued rGT (% choice) CPT (% choice) P1 P2 P3 P4 P1 P2 P3 P4 P1 P2 P3 P4 BL 8.19 ± 1.86 69.26 ± 5.96 5.11 ± 1.38 17.44 ± 6.45 6.13 ± 1.54 44.57 ± 7.62 28.68 ± 8.01 20.63 ± 6.91 26.26 ± 4.75 17.62 ± 3.13 23.62 ± 3.58 32.50 ± 5.15 Amph-vehicle 11.25 ± 2.75 60.96 ± 7.21 5.51 ± 1.51 22.29 ± 7.71 12.85 ± 5.24 42.29 ± 7.80 25.86 ± 7.00 19.00 ± 5.60 Amph 0.5 20.04 ± 4.28 49.77 ± 6.74 10.43 ± 4.64 19.75 ± 7.05 14.0 ± 3.35 40.52 ± 6.55 24.31 ± 6.47 20.85 ± 5.93 Amph 1.0 2.37 ± 6.27 41.34 ± 5.13 7.74 ± 2.05 18.55 ± 5.52 26.54 ± 4.80 27.81 ± 4.46 21.36 ± 4.84 24.29 ± 5.54 Amph 1.5 39.85 ± 7.03 31.51 ± 4.09 7.86 ± 3.12 20.77 ± 6.13 25.80 ± 5.44 33.80 ± 5.07 21.20 ± 5.92 19.21 ± 4.11 PD vehicle 3.24 ± 0.81 68.13 ± 10.2 5.99 ± 3.06 22.64 ± 11.0 5.49 ± 2.37 44.59 ± 14.3 29.47 ± 14.08 20.45 ± 13.3 28.06 ± 5.98 22.00 ± 5.10 20.07 ± 4.70 29.87 ± 6.89 PD 0.01 3.93 ± 0.74 69.69 ± 9.85 3.04 ± 1.09 23.34 ± 11.1 5.78 ± 2.45 38.91 ± 11.5 35.45 ± 13.89 19.85 ± 12.4 29.35 ± 7.24 23.37 ± 5.73 17.48 ± 3.60 29.79 ± 6.60 PD 0.03 3.41 ± 0.89 66.42 ± 10.50 4.64 ± 2.34 25.53 ± 11.3 5.36 ± 2.58 39.81 ± 12.9 34.85 ± 13.56 19.98 ± 13.0 28.26 ± 7.27 24.83 ± 5.72 17.70 ± 3.99 29.22 ± 6.80 PD 0.1 2.08 ± 0.75 71.21 ± 10.25 3.81 ± 1.90 22.89 ± 11.0 4.11 ± 1.04 41.53 ± 13.5 33.96 ± 14.52 20.39 ± 12.8 24.42 ± 7.09 26.95 ± 6.61 17.01 ± 4.58 31.62 ± 7.45 SB vehicle 3.63 ± 1.45 64.20 ± 11.79 4.08 ± 2.04 28.09 ± 13.2 6.20 ± 2.91 35.65 ± 12.3 36.01 ± 13.52 22.13 ± 14.3 31.09 ± 6.62 21.89 ± 4.90 17.54 ± 3.41 29.49 ± 6.49 SB 0.5 3.03 ± 1.37 68.67 ± 9.44 3.83 ± 1.95 24.47 ± 10.9 6.62 ± 4.31 35.76 ± 13.9 34.30 ± 14.60 23.32 ± 15.0 31.13 ± 5.95 21.99 ± 5.59 17.28 ± 3.92 29.60 ± 5.78 SB 1.0 4.87 ± 2.78 64.90 ± 10.44 4.34 ± 3.57 25.89 ± 11.7 7.49 ± 3.88 41.91 ± 13.6 28.59 ± 13.51 22.00 ± 14.4 29.82 ± 6.36 16.04 ± 4.05 21.38 ± 3.70 32.76 ± 6.59 SB 5.0 2.53 ± 0.76 67.52 ± 9.77 4.77 ± 2.58 25.18 ± 10.9 5.14 ± 2.03 35.25 ± 12.7 38.31 ± 13.98 21.30 ± 13.1 30.45 ± 6.08 18.88 ± 4.78 20.39 ± 4.76 30.28 ± 6.88 Significant within-subject differences from vehicle are noted in bold. Data shown are group mean ± SEM. Note that the SEM reflects variation between subjects and is therefore not a reliable indication of the size of a within-subjects drug effect.
