Introduction
Materials and Methods
Animals and Treatments
Drugs
Behavioral Study
Locomotor Activity
Biochemical Studies
Ex Vivo Experiments
DA Metabolism and l-DOPA Metabolism
Assessment of Caspase-3 Activity
In Vivo Microdialysis
Calculations and Statistics
Results
Behavioral Study
The Effect of Acute 1BnTIQ Administration on l-DOPA-Induced Hyperactivity in Rats
The Effect of Chronic 1BnTIQ Administration on l-DOPA-Induced Hyperactivity in Rats
Biochemical Studies: Ex Vivo Experiments
The Effect of Acute 1BnTIQ Administration on l-DOPA-Induced Changes on DA Metabolism in Rat Brain Structures
Substantia Nigra
Treatment acute | Treatment acute | DA (ng/g tissue) | DOPAC (ng/g tissue) | 3-MT (ng/g tissue) | HVA (ng/g tissue) | HVA/DA | |
---|---|---|---|---|---|---|---|
Substantia Nigra | |||||||
Saline | Saline | 938 ± 100 | 216 ± 17 | 45 ± 4 | 111 ± 10 | 12 ± 1 | |
Saline |
l-DOPA 100 | 7438 ± 2071** | 20649 ± 5208** | 162 ± 25** | 4701 ± 695** | 93 ± 36* | |
1BnTIQ 25 | Saline | 534 ± 67++
| 147 ± 10++
| 24 ± 4++
| 91 ± 5++
| 18 ± 2 | |
1BnTIQ 50 | Saline | 566 ± 47++
| 171 ± 27++
| 27 ± 4++
| 101 ± 15++
| 18 ± 2 | |
1BnTIQ 25 |
l-DOPA 100 | 869 ± 108++
| 873 ± 273++
| 54 ± 13++
| 755 ± 300++
| 88 ± 33 | |
1BnTIQ 50 |
l-DOPA 100 | 774 ± 93++
| 1013 ± 493++
| 44 ± 6++
| 935 ± 466++
| 108 ± 40* | |
Effect of 1BnTIQ |
F
(2/29) = 10.8
P < 0.01 |
F
(2/29) = 13.5
P < 0.01 |
F
(2/29) = 19.3
P < 0.01 |
F
(2/29) = 18.7
P < 0.01 |
F
(2/29) = 0.1 N.S. | ||
Effect of l-DOPA |
F
(2/29) = 10.7
P < 0.01 |
F
(2/29) = 16.5
P < 0.01 |
F
(2/29) = 28.9
P < 0.01 |
F
(2/29) = 45.6
P < 0.01 |
F
(2/29) = 14.8
P < 0.01 | ||
Interaction of 1BnTIQ + l-DOPA |
F
(2/29) = 8.55
P < 0.01 |
F
(2/29) = 13.4
P < 0.01 |
F
(2/29) = 10.1
P < 0.01 |
F
(2/29) = 18.4
P < 0.01 |
F
(2/29) = 0.1 N.S. | ||
Striatum | |||||||
Saline | Saline | 8691 ± 265 | 1098 ± 43 | 380 ± 7 | 713 ± 26 | 8.2 ± 0.3 | |
Saline |
l-DOPA 100 | 25191 ± 3967** | 23040 ± 6005** | 281 ± 26** | 6238 ± 944** | 28.1 ± 7.9* | |
1BnTIQ 25 | Saline | 6976 ± 389++
| 1428 ± 132++
| 348 ± 25+
| 1065 ± 176++
| 15.3 ± 2.4 | |
1BnTIQ 50 | Saline | 5246 ± 411++
| 1187 ± 86++
| 271 ± 8** | 907 ± 137++
| 18.2 ± 3.7 | |
1BnTIQ 25 |
l-DOPA 100 | 6669 ± 389++
| 2021 ± 373++
| 284 ± 12** | 1865 ± 414++
| 28 ± 5.6* | |
1BnTIQ 50 |
l-DOPA 100 | 5945 ± 646++
| 2330 ± 641++
| 252 ± 17** | 2469 ± 755*++
| 41.8 ± 10.5** | |
Effect of 1BnTIQ |
F
(2/29) = 26.7
P < 0.01 |
F
(2/29) = 11.1
P < 0.01 |
F
(2/29) = 8.5
P < 0.01 |
F
(2/29) = 8.5
P < 0.01 |
F
(2/29) = 2.0 N.S. | ||
Effect of l-DOPA |
F
(2/29) = 16.0
P < 0.01 |
F
(2/29) = 14.3
P < 0.01 |
F
(2/29) = 17.4
P < 0.01 |
F
(2/29) = 35.8
P < 0.01 |
F
(2/29) = 13.8
P < 0.01 | ||
Interaction of 1BnTIQ + l-DOPA |
F
(2/29) = 15.2
P < 0.01 |
F
(2/29) = 11.5
P < 0.01 |
F
(2/29) = 2.5 N.S. |
F
(2/29) = 11.2
P < 0.01 |
F
(2/29) = 0.4 N.S. |
Striatum
Substantia Nigra
Treatment chronic | Treatment acute | DA (ng/g tissue) | DOPAC (ng/g tissue) | 3-MT (ng/g tissue) | HVA (ng/g tissue) | HVA/DA | ||
---|---|---|---|---|---|---|---|---|
Substantia nigra | ||||||||
Saline | Saline | 564 ± 44 | 206 ± 39 | 37 ± 2 | 84 ± 9 | 15 ± 2 | ||
Saline |
l-DOPA 100 | 5556 ± 1015** | 25178 ± 5309** | 181 ± 24** | 6410 ± 641** | 129 ± 16** | ||
1BnTIQ 25 | Saline | 502 ± 23++
| 174 ± 11++
| 40 ± 3++
| 83 ± 7++
| 17 ± 2 | ||
1BnTIQ 50 | Saline | 413 ± 16++
| 180 ± 16++
| 32 ± 2++
| 99 ± 8++
| 24 ± 2 | ||
1BnTIQ 25 |
l-DOPA 100 | 1272 ± 180+
| 2210 ± 628++
| 89 ± 11++
| 1864 ± 514++
| 128 ± 30** | ||
1BnTIQ 50 |
l-DOPA 100 | 3987 ± 2414* | 8142 ± 4355++
| 142 ± 45** | 4080 ± 1394**+
| 181 ± 30** | ||
Effect of 1BnTIQ |
F
(2/30) = 2.08 N.S. |
F
(2/30) = 8.99
P < 0.01 |
F
(2/30) = 2.22 N.S. |
F
(2/30) = 5.92
P < 0.01 |
F
(2/30) = 0.1 N.S. | |||
Effect of l-DOPA |
F
(2/30) = 12.64
P < 0.01 |
F
(2/30) = 25.72
P < 0.01 |
F
(2/30) = 34.24
P < 0.01 |
F
(2/30) = 55.78
P < 0.01 |
F
(2/30) = 14.8
P < 0.01 | |||
Interaction of 1BnTIQ + l-DOPA |
F
(2/30) = 2.00 N.S. |
F
(2/30) = 8.94
P < 0.01 |
F
(2/30) = 2.55 N.S. |
F
(2/30) = 5.92
P < 0.01 |
F
(2/30) = 0.1 N.S. | |||
Striatum | ||||||||
Saline | Saline | 9793 ± 426 | 1486 ± 122 | 383 ± 16 | 701 ± 34 | 7.2 ± 0.3 | ||
Saline |
l-DOPA 100 | 25128 ± 2755** | 33727 ± 6080** | 269 ± 16** | 9696 ± 870** | 39.5 ± 2.4** | ||
1BnTIQ 25 | Saline | 7645 ± 525++
| 1142 ± 84++
| 410 ± 21++
| 735 ± 57++
| 9.9 ± 1.1++
| ||
1BnTIQ 50 | Saline | 6042 ± 348+
| 1415 ± 147++
| 335 ± 14++
| 1111 ± 104++
| 18.6 ± 1.8**++
| ||
1BnTIQ 25 |
l-DOPA 100 | 14653 ± 3192++
| 4283 ± 922++
| 330 ± 15*+
| 3634 ± 769*++
| 25.1 ± 4.6**++
| ||
1BnTIQ 50 |
l-DOPA 100 | 18281 ± 5335** | 3318 ± 550++
| 338 ± 13++
| 7452 ± 1903** | 42.6 ± 2.3** | ||
Effect of 1BnTIQ |
F
(2/30) = 2.94 N.S. |
F
(2/30) = 23.8
P < 0.01 |
F
(2/30) = 4.18
P < 0.05 |
F
(2/30) = 5.75
P < 0.01 |
F
(2/30) = 14.0
P < 0.01 | |||
Effect of l-DOPA |
F
(2/30) = 25.54
P < 0.01 |
F
(2/30) = 36.4
P < 0.01 |
F
(2/30) = 23.67
P < 0.01 |
F
(2/30) = 66.71
P < 0.01 |
F
(2/30) = 138
P < 0.01 | |||
Interaction of 1BnTIQ + l-DOPA |
F
(2/30) = 1.13 N.S. |
F
(2/30) = 23.2
P < 0.01 |
F
(2/30) = 7.16
P < 0.01 |
F
(2/30) = 5.62
P < 0.01 | F(2/30) = 5.9
P < 0.01 |
Striatum
The Effect of Acute and Chronic Administration of 1BnTIQ on l-DOPA Metabolism in Rat Striatum
Treatment acute | Treatment acute | 3-MDOPA (ng/g tissue) |
---|---|---|
Saline | Saline | 1.5 ± 0.19 |
Saline |
l-DOPA 100 | 48687 ± 8801** |
1BnTIQ 50 | Saline | 1.43 ± 0.17 |
1BnTIQ 50 |
l-DOPA 100 | 15125 ± 3468++
|
Effect of 1BnTIQ |
F
(1/18) = 7.38
P < 0.05 | |
Effect of l-DOPA |
F
(1/18) = 26.7
P < 0.01 | |
Interaction of 1BnTIQ + l-DOPA |
F
(1/18) = 7.38
P < 0.05 |
Treatment
chronic | Treatment
acute | 3-MDOPA
(ng/g tissue) |
---|---|---|
Saline | Saline | 1.49 ± 0.22 |
Saline |
l-DOPA 100 | 26868 ± 3867** |
1BnTIQ 25 | Saline | 1.52 ± 0.24 |
1BnTIQ 50 | Saline | 1.17 ± 0.12 |
1BnTIQ 25 |
l-DOPA 100 | 8381 ± 1714++
|
1BnTIQ 50 |
l-DOPA 100 | 18635 ± 4868**+
|
Effect of 1BnTIQ |
F
(2/30) = 6.18
P < 0.01 | |
Effect of l-DOPA |
F
(2/30) = 69.78
P < 0.01 | |
Interaction of 1BnTIQ + l-DOPA |
F
(2/30) = 6.19
P < 0.01 |