ABSTRACT
Dopamine replacement therapy (DRT) reduces motor symptoms in Parkinson's disease (PD), but also induces impulsive-compulsive behavior (ICB) in up to 25% of PD patients. These non-motor side effects of DRT generally follow a gradual transition from impulsive to compulsive-like-i.e. repetitive, compelled, and non-pleasurable-behavior. Here, we investigated the effect of chronic pramipexole (PPX) treatment on the onset of compulsive-like behavior, measured via the post-training signal attenuation (PTSA) procedure, in rats with dopaminergic lesions. Accordingly, we aimed to mimic chronic DRT in a PD context, and obtain data on the brain regions that potentially sustain this type of compulsive behavior pattern in rats. We observed that the lesion or treatment alone did not induce compulsive lever pressing in rats. However, rats with lesions of the substantia nigra and ventral tegmental area as well as with chronic PPX treatment developed strong compulsive lever-pressing behavior, as measured via PTSA. Furthermore, when chronic PPX treatment was discontinued before the PTSA test, the lesioned rats showed the same level of compulsive behavior as sham-operated rats. In fact, lesioned, treated, and compulsive-like rats showed significantly higher Fos expression in the orbitofrontal cortex and dorsal striatum. Thus, chronic PPX treatment in PD rats induced a strong compulsive-like behavior. Furthermore, Fos expression mapping suggests that the behavior was sustained via the activation of the orbitofrontal cortex and dorsal striatum.
Subject(s)
Antiparkinson Agents/adverse effects , Benzothiazoles/adverse effects , Compulsive Behavior/chemically induced , Parkinsonian Disorders/drug therapy , Animals , Antiparkinson Agents/pharmacology , Benzothiazoles/pharmacology , Compulsive Behavior/physiopathology , Corpus Striatum/drug effects , Corpus Striatum/metabolism , Corpus Striatum/pathology , Frontal Lobe/drug effects , Frontal Lobe/metabolism , Frontal Lobe/pathology , Immunohistochemistry , Male , Motor Activity/drug effects , Motor Activity/physiology , Oxidopamine , Parkinsonian Disorders/pathology , Parkinsonian Disorders/physiopathology , Pramipexole , Proto-Oncogene Proteins c-fos/metabolism , Random Allocation , Rats, Sprague-Dawley , Substantia Nigra/drug effects , Substantia Nigra/pathology , Substantia Nigra/physiopathology , Ventral Tegmental Area/drug effects , Ventral Tegmental Area/pathology , Ventral Tegmental Area/physiopathologyABSTRACT
A study was made of iatrogenic complications (IC) occurring in the department of cardiology of the Nantes Teaching Hospital Group between May 31, 1990 and June 1, 1991. One hundred and fifty eight IC were seen during this period, i.e. an annual incidence of 4.4%. There were 4 deaths following and IC, i.e. an annual mortality rate of 0.11%. Five other IC had serious though non-fatal consequences. Taken in general, IC appeared to be benign and of various origins. Drugs were responsible for almost half of IC and invasive investigations for one third. Application of a simple and single preventive approach is difficult in view of the diversity of causes. The solution lies in part in awareness and education concerning the problem, in which a permanent register system like ours certainly has a role to play.
