Figure legends
Figure 1. Behavioral and neurochemical effects of reverse dialysis of telenzepine in the dopamine-depleted striatum of dyskinetic rats undergoing microdialysis. Dyskinetic rats were implanted with one probe in the lesioned dorsolateral striatum and another in ipsilateral substantia nigra reticulata (SNr). Twenty-four hours later, rats received an acute challenge with L-DOPA alone (6 mg kg-1 plus 12 mg kg-1 benserazide, i.p.) or in combination with telenzepine (100 nM) through the probe. Telenzepine perfusion started 40 min prior to L-DOPA administration and continued until the end of experiment. A group treated with telenzepine alone was also included. ALO AIMs were scored for 1 min every 20 min over 120 min after L-DOPA administration, then cumulative ALO AIMs calculated (A). Dialysate samples were collected every 20 min for 120 min after L-DOPA administration, and GABA (B) and glutamate (Glu; C-D) levels in dialysates were monitored in SNr and striatum. Data are means ± SEM of 8 rats per group. Data were statistically analyzed as cumulative ALO AIMs score using the Mann-Whitney test (A) or as AUC values using ANOVA followed by the Newman-Keuls test (B-D). *p<0.05 different from Ringer + L-DOPA 6 mg Kg-1; °p<0.05, °°p<0.01, different from Telenzepine 100 nM + saline.
Figure 2. Behavioral and neurochemical effects of reverse dialysis of PD-102807 in the dopamine-depleted striatum of dyskinetic rats undergoing microdialysis. Dyskinetic rats were implanted with one probe in the lesioned dorsolateral striatum and another in ipsilateral substantia nigra reticulata (SNr). Twenty-four hours later, rats received an acute challenge with L-DOPA alone (6 mg kg-1 plus 12 mg kg-1 benserazide, i.p.) or in combination with PD-102807 (3 µM) through the probe. PD-102807 perfusion started 40 min prior to L-DOPA administration and continued until the end of experiment. A group treated with PD-102807 alone was also included. ALO AIMs were scored for 1 min every 20 min over 120 min after L-DOPA administration, then cumulative ALO AIMs calculated (A). Dialysate samples were collected every 20 min for 120 min after L-DOPA administration, and GABA (B) and glutamate (Glu; C-D) levels in dialysates were monitored in SNr and striatum. Data are means ± SEM of 8 rats per group. Data were statistically analyzed as cumulative ALO AIMs score using the Mann-Whitney test (A) or as AUC values using ANOVA followed by the Newman-Keuls test (B-D). **p<0.01 different from Ringer + L-DOPA 6 mg Kg-1; °°p<0.01, different from PD-102807 3 µM + saline.
Figure 3. Behavioral and neurochemical effects of reverse dialysis of tropicamide in the dopamine-depleted striatum of dyskinetic rats undergoing microdialysis. Dyskinetic rats were implanted with one probe in the lesioned dorsolateral striatum and another in ipsilateral substantia nigra reticulata (SNr). Twenty-four hours later, rats received an acute challenge with L-DOPA alone (6 mg kg-1 plus 12 mg kg-1 benserazide, i.p.) or in combination with tropicamide (100 nM) through the probe. Tropicamide perfusion started 40 min prior to L-DOPA administration and continued until the end of experiment. A group treated with tropicamide alone was also included. ALO AIMs were scored for 1 min every 20 min over 120 min after L-DOPA administration, then cumulative ALO AIMs calculated (A). Dialysate samples were collected every 20 min for 120 min after L-DOPA administration, and GABA (B) and glutamate (Glu; C-D) levels in dialysates were monitored in SNr and striatum. Data are means ± SEM of 8 rats per group. Data were statistically analyzed as cumulative ALO AIMs score using the Mann-Whitney test (A) or as AUC values using ANOVA followed by the Newman-Keuls test (B-D). *p<0.05, **p<0.01, different from Ringer + L-DOPA 6 mg Kg-1; °°p<0.01, different from Tropicamide 100 nM + saline.
Figure 4. Behavioral and neurochemical effects of reverse dialysis of VU0152100 in the dopamine-depleted striatum of dyskinetic rats undergoing microdialysis. Dyskinetic rats were implanted with one probe in the lesioned dorsolateral striatum and another in ipsilateral substantia nigra reticulata (SNr). Twenty-four hours later, rats received an acute challenge with L-DOPA alone (6 mg kg-1 plus 12 mg kg-1 benserazide, i.p.) or in combination with VU0152100 (100 µM) through the probe. VU0152100 perfusion started 40 min prior to L-DOPA administration and continued until the end of experiment. A group treated with VU0152100 alone was also included. ALO AIMs were scored for 1 min every 20 min over 120 min after L-DOPA administration, then cumulative ALO AIMs calculated (A). Dialysate samples were collected every 20 min for 120 min after L-DOPA administration, and GABA (B) and glutamate (Glu; C-D) levels in dialysates were monitored in SNr and striatum. Data are means ± SEM of 8 rats per group. Data were statistically analyzed as cumulative ALO AIMs score using the Mann-Whitney test (A) or as AUC values using ANOVA followed by the Newman-Keuls test (B-D). *p<0.05; **p<0.01 different from Ringer + L-DOPA 6 mg Kg-1; °p<0.05, °°p<0.01, different from VU0152100 100 µM + saline.
Figure 5. Behavioral and neurochemical effects of reverse dialysis of AFDX-116 in the dopamine-depleted striatum of dyskinetic rats undergoing microdialysis. Dyskinetic rats were implanted with one probe in the lesioned dorsolateral striatum and another in ipsilateral substantia nigra reticulata (SNr). Twenty-four hours later, rats received an acute challenge with L-DOPA alone (6 mg kg-1 plus 12 mg kg-1 benserazide, i.p.) or in combination with AFDX-116 (200 nM) or AFDX-116 (200 nM) + PD-102807 (3 µM) through the probe. PD-102807 perfusion started 40 min prior to L-DOPA administration whereas perfusion with AFDX-116 started 60 min prior to L-DOPA or 20 min prior to PD-102807 and continued until the end of experiment. A group treated with AFDX-116 alone was also included. ALO AIMs were scored for 1 min every 20 min over 120 min after L-DOPA administration, then cumulative ALO AIMs calculated (A). Dialysate samples were collected every 20 min for 120 min after L-DOPA administration, and GABA (B) and glutamate (C-D) levels in dialysates were monitored in striatum and SNr. Data are means ± SEM of 8 rats per group. Data were statistically analyzed as cumulative ALO AIMs score using the the Mann-Whitney test (A) or as AUC values using ANOVA followed by the Newman-Keuls test (B-F). *p<0.05, **p<0.01 different from Ringer + L-DOPA; #p<0.05 different from PD-102807 3 µM + L-DOPA; °p<0.05; °°p<0.01 different from VU0152100 100 µM + saline (B-D) or PD-102807 3 µM + saline (E-F).
Figure 6. Behavioral and neurochemical effects of reverse dialysis of VU0152100 or PD-102807 in the substantia nigra pars reticulata (SNr) of dyskinetic rats undergoing microdialysis. Dyskinetic rats were implanted with one probe in the lesioned dorsolateral striatum and another in ipsilateral SNr. Twenty-four hours later, rats received an acute challenge with L-DOPA alone (6 mg kg-1 plus 12 mg kg-1 benserazide, i.p.) or in combination with VU0152100 (100 µM) or PD-102807 (3 µM) through the nigral probe. VU0152100 or PD-102807 perfusion started 40 min prior to L-DOPA administration and continued until the end of experiment. A group treated with VU0152100 or PD-102807 alone were also included. ALO AIMs were scored for 1 min every 20 min over 120 min after L-DOPA administration, then cumulative ALO AIMs calculated (A). Dialysate samples were collected every 20 min for 120 min after L-DOPA administration, and GABA (B, E) and glutamate (Glu; B-F) levels in dialysates were monitored in SNr or striatum. Data are means ± SEM of 8 rats per group. Data were statistically analyzed as cumulative ALO AIMs score using the Kruskal-Wallis test for non parametric ANOVA followed by the Dunn test (A) or as AUC values using ANOVA followed by the Newman-Keuls test (B-F) *p<0.05, **p<0.01 different from Ringer + L-DOPA; #p<0.05 different from PD-102807 3 µM + L-DOPA; °p<0.05; °°p<0.01 different from VU0152100 100 µM + saline (B-D) or PD-102807 3 µM + saline (E-F).