Article Figures & Data
Figures
- Fig. 1.
Effects of cariprazine on the extracellular levels of neurotransmitters and metabolites in the rat NAC and HIP. (A and B) Area under the curve values. N = 8 per group. Cariprazine was administered at the 0-minute time point. *P < 0.05; **P < 0.01; ***P < 0.001 vs. vehicle; one-way ANOVA least significant difference. Cariprazine 0.1 mg/kg, but not 0.03 mg/kg (PO), significantly increased DA [P = 0.001 (C)], NE (P = 0.040), 5-HT [P = 0.035 (D)], and Gly (P = 0.021) efflux in the NAC; cariprazine also increased DA [P = 0.001 (E)], 5-HT [P = 0.006 (F)], DOPAC (P = 0.027), and HVA (P = 0.025) efflux in the HIP. Cariprazine 0.3 mg/kg increased DA [P < 0.001 (C)], NE (P = 0.003), Gly (P = 0.026), and Glu (P = 0.021) efflux in the NAC. It also increased HIP DA [P = 0.004 (E)] and NE (P = 0.025) as well as DOPAC (P = 0.002) efflux. Cariprazine had no effect on ACh, Ser, or GABA efflux in either region. AUC, area under the curve.
- Fig. 2.
Effect of SB-277011A and (+)-PD-128907 on neurotransmitter levels in the rat NAC and HIP. (A and B) Area under the curve values. N = 8 per group. SB-277011A was administered at the 0-minute time point, and (+)-PD-128907 was administered at the −30-minute time point. *P < 0.05; **P < 0.01; ***P < 0.001 vs. vehicle; +P < 0.05; ++P < 0.01; +++P < 0.001 vs. SB-277011A in one-way ANOVA least significant difference. The DA D3 receptor antagonist SB-277011A (10 mg/kg, i.p.) significantly increased DA [P < 0.001 (D)], NE (P = 0.003), DOPAC (P = 0.003), HVA (P = 0.001), 5-HIAA (P = 0.018), Gly (P = 0.039), and Glu (P = 0.016), but not ACh (C) efflux in the NAC (A), as well as ACh [P = 0.007 (E)], DA [P < 0.001 (F)], NE (P < 0.001), DOPAC (P < 0.001), HVA (P = 0.026), and 5-HIAA (P = 0.005) efflux in the HIP (B). The DA D3 receptor agonist (+)-PD-128907 (0.03 mg/kg, i.p.) slightly decreased HIP NE (P = 0.022) efflux, with no effect on other neurotransmitters. (+)-PD-128907 partially, but significantly, blocked the SB-277011A–induced increase on DA efflux in the NAC [P < 0.001 (A)] and HIP [P = 0.004 (B)] and NE efflux in the NAC [P = 0.022 (A)] and HIP [P = 0.001 (B)]. AUC, area under the curve.
- Fig. 3.
Effect of cariprazine and (+)-PD-128907 on neurotransmitter levels in the rat NAC and HIP. (A and B) Area under the curve values. N = 8 per group, except N = 7 for (+)-PD-128907+cariprazine group. Cariprazine was administered at the 0-minute time point, and (+)-PD-128907 was administered at the −30-minute time point. *P < 0.05; **P < 0.01 vs. vehicle; +P < 0.05; ++P < 0.01 vs. cariprazine in one-way ANOVA least significant difference. (+)-PD-128907 partially but significantly blocked the effects of cariprazine (0.1 mg/kg) on DA efflux (P = 0.033) in the NAC (A) and NE efflux (P = 0.009) in the HIP (B). AUC, area under the curve. Time response curves for DA and 5-HT in NAC and HIP are given in C, D, and E, F, respectively.
Tables
NAC HIP nM nM ACh 1.37 ± 0.05 1.36 ± 0.06 DA 1.65 ± 0.06 1.11 ± 0.07 5-HT 1.22 ± 0.05 1.23 ± 0.05 NE 2.15 ± 0.10 2.08 ± 0.08 DOPAC 3467.55 ± 136.54 293.64 ± 15.32 HVA 2814.42 ± 82.48 261.45 ± 10.41 5-HIAA 3026.48 ± 131.14 2776.67 ± 132.42 Ser 5362.21 ± 198.10 5577.61 ± 244.77 Gly 1308.44 ± 56.22 2564.08 ± 118.66 Glu 1357.62 ± 61.57 1197.97 ± 51.43 GABA 131.77 ± 4.68 158.77 ± 8.06 ACh, acetylcholine; DA, dopamine; DOPAC, 3,4-dihydroxyphenylacetic acid; GABA, gamma-aminobutyric acid; Glu, glutamate; Gly, glycine; 5-HIAA, 5-hydroxyindole acetic acid; HIP, hippocampus; 5-HT, serotonin; HVA, homovanillic acid; NAC, nucleus accumbens; NE, norepinephrine; SE, standard error; Ser, serine.
ACh DA 5-HT NE DOPAC HVA 5-HIAA Ser Gly Glu GABA NAC Cariprazine 0.03 mg/kg — — — — — — — — — — — Cariprazine 0.1 mg/kg — I I I — — — — I — — Cariprazine 0.3 mg/kg — I — I — — — — I I — (+)-PD-128907 0.03 mg/kg — — — — — — — — — — — SB-277011A 10 mg/kg — I — I I I I — I I — (+)-PD-128907+SB-277011A 0.03 mg/kg+10 mg/kg — I — — — — — — — — — (+)-PD-128907+cariprazine 0.03 mg/kg+0.1 mg/kg — — — — — — — — — — — HIP Cariprazine 0.03 mg/kg — — — — — — — — — — — Cariprazine 0.1 mg/kg — I I — I I — — — — — Cariprazine 0.3 mg/kg — I — I I — — — — — — (+)-PD-128907 0.03 mg/kg — — — D — — — — — — — SB-277011A 10 mg/kg I I — I I I I — — — D (+)-PD-128907+SB-277011A 0.03 mg/kg+10 mg/kg I I — — — I — — — — — (+)-PD-128907+cariprazine 0.03 mg/kg+0.1 mg/kg — — — — — — — — — — — D, decrease; I, increase; —, no effect.
In this issue
Cariprazine Increases Dopamine and Serotonin Efflux
