| Autor: |
Michel Engeln, Serge H. Ahmed, Caroline Vouillac, François Tison, Erwan Bezard, Pierre-Olivier Fernagut |
| Jazyk: |
angličtina |
| Rok vydání: |
2013 |
| Předmět: |
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| Zdroj: |
Neurobiology of Disease, Vol 49, Iss , Pp 79-86 (2013) |
| Druh dokumentu: |
article |
| ISSN: |
1095-953X |
| DOI: |
10.1016/j.nbd.2012.08.005 |
| Popis: |
Striatal D2 and D3 dopamine receptors are involved in mediating the reinforcing properties of natural rewards and drugs. In Parkinson's disease, while D2/3 dopamine agonists alleviate motor symptoms, behavioral addictions and withdrawal syndrome are reported in up to 15% of patients. The origin of such adverse effects is poorly understood but suggests that D2/3 agonists could possess reinforcing properties. We evaluated the reinforcing properties of the widely used D2/3 agonist, Pramipexole (PPX), in normal and parkinsonian rats. Intracerebroventricular injections of 6-OHDA induced a bilateral loss of tyrosine hydroxylase-positive cells in the substantia nigra (−51%) and ventral tegmental area (−31%). The animals were then allowed to self-administer intravenous PPX under fixed ratio and progressive ratio (PR) reinforcement schedules before being tested for extinction of PPX seeking. While parkinsonian were slower than sham rats in acquiring self-administration behavior, they later reached the same level of intake. The reinforcing value of PPX, as assessed during PR and extinction, was moderate in both groups. PPX heightened ∆FosB expression in dorsal striatum of lesioned rats and similar PR results involved different striatal subregions between groups. Altogether, our results show that drug-naïve rats self-administer PPX and that the dopaminergic lesion does not affect its reinforcing effects. While PPX reinforcing value was moderate in most rats, a subset of animals displayed a high number of responses and appeared to be particularly sensitive to this drug. These data suggest that PPX may not be responsible for the reported side-effects but rather call for further investigating the differential vulnerability among individuals. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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