Dopamine stimulation via infusion in the lateral ventricle.
Continuous dopamine (DA) stimulation is a therapeutic approach that applies to the treatment of motor fluctuations due to pulsatile DA stimulation in Parkinson's disease (PD), to cure the abuse of drugs, such as cocaine or amphetamine (which produce short-lasting peaks of extracellular DA), and as a safe therapeutic approach to avoid hedonistic homeostatic dysregulation (which sometime develops as an abuse pattern in PD patients receiving a pulsatile DA replacement therapy). However, systemic continuous delivery of DA agonists leads to a variety of side effects. In search for an alterative approach, in the present study we evaluated the possibility of delivering intracerebroventricularly (i.c.v.), a DA agonist: lisuride that was already shown to be effective when administered continuously subcutaneously (s.c.). In particular, we were interested in examining whether lisuride infused within the lateral ventricle was still able to stimulate DA receptor by inducing contralateral turning behavior in hemiparkinsonian rats. We found that lisuride, when infused in the lateral ventricle was effective in reducing the threshold for stimulating DA receptors. These results offer a more reliable and safe therapeutic approach to deliver continuous DA selectively in the brain.
Biagioni
Francesca
F
Department of Human Morphology and Applied Biology, University of Pisa, Via Roma, 55, I-56126 Pisa, Italy.
Busceti
Carla L
CL
Molinaro
Gemma
G
Battaglia
Giuseppe
G
Giorgi
Filippo S
FS
Ruggieri
Stefano
S
Fornai
Francesco
F
D000818:Animals; D018491:Dopamine Agonists / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D004347:Drug Interactions; D007260:Infusion Pumps; D007276:Injections, Intraventricular; D020547:Lateral Ventricles / Q000187:drug effects*; D008090:Lisuride / Q000008:administration & dosage*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D016627:Oxidopamine / Q000008:administration & dosage; D020734:Parkinsonian Disorders / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar; D011954:Receptors, Dopamine / Q000378:metabolism*
D018491:Dopamine Agonists; D011954:Receptors, Dopamine; D016627:Oxidopamine; D008090:Lisuride