Reinforcing properties of Pramipexole in normal and parkinsonian rats.
Neurobiology of Disease. 2013-01-01; 49: 79-86
DOI: 10.1016/j.nbd.2012.08.005
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1. Neurobiol Dis. 2013 Jan;49:79-86. doi: 10.1016/j.nbd.2012.08.005. Epub 2012 Aug
23.
Reinforcing properties of Pramipexole in normal and parkinsonian rats.
Engeln M(1), Ahmed SH(1), Vouillac C(1), Tison F(2), Bezard E(2), Fernagut PO(3).
Author information:
(1)Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, F-33000
Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293,
F-33000 Bordeaux, France.
(2)Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, F-33000
Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293,
F-33000 Bordeaux, France; Service de Neurologie, CHU de Bordeaux, F-33604 Pessac,
France.
(3)Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, F-33000
Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293,
F-33000 Bordeaux, France. Electronic address:
.
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.
Copyright © 2012 Elsevier Inc. All rights reserved.
DOI: 10.1016/j.nbd.2012.08.005
PMID: 22940424 [Indexed for MEDLINE]