title: Reinforcing properties of Pramipexole in normal and parkinsonian rats.
abstract: 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.
authors.affiliation: Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Engeln
authors.affiliation: Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France.
authors.forename: Serge H
authors.initials: SH
authors.lastname: Ahmed
authors.affiliation: Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Vouillac
authors.affiliation: 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.
authors.forename: François
authors.initials: F
authors.lastname: Tison
authors.affiliation: 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.
authors.forename: Erwan
authors.initials: E
authors.lastname: Bezard
authors.affiliation: 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: pierre-olivier.fernagut@u-bordeaux2.fr.
authors.forename: Pierre-Olivier
authors.initials: PO
authors.lastname: Fernagut
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000008:administration & dosage*; D052160:Benzothiazoles / Q000008:administration & dosage*; D003342:Corpus Striatum / Q000187:drug effects / Q000503:physiopathology; D018491:Dopamine Agonists / Q000494:pharmacology*; D058999:Drug-Seeking Behavior / Q000502:physiology*; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology; D007150:Immunohistochemistry; D008297:Male; D009043:Motor Activity / Q000502:physiology; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000503:physiopathology; D000077487:Pramipexole; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000378:metabolism; D050637:Receptors, Dopamine D3 / Q000819:agonists / Q000378:metabolism; D012055:Reinforcement Schedule; D012646:Self Administration; D019966:Substance-Related Disorders / Q000503:physiopathology*
chemical_list: D000978:Antiparkinson Agents; D052160:Benzothiazoles; D018491:Dopamine Agonists; C483820:Fosb protein, rat; D016760:Proto-Oncogene Proteins c-fos; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D000077487:Pramipexole; D016627:Oxidopamine