Blockade of adenosine A2A receptors antagonizes parkinsonian tremor in the rat tacrine model by an action on specific striatal regions.
Acute administration of the acetylcholinesterase inhibitor tacrine to rats induces tremulous jaw movements which can be used as a valuable model of parkinsonian tremor. In the present study, the number of tremor episodes and jaw movements were evaluated to assess the effects of the selective A2A antagonists SCH 58261 and SCH BT2 on tremorgenesis. SCH 58261 dose-dependently, and maximally at 5 mg/kg, reduced the number of both tremor episodes (-35%) and jaw movements (-50%), induced in rats by tacrine (2.5 mg/kg ip). Since adenosine A2A receptors are largely expressed throughout the striatum, chronic cannulae were implanted in the rat dorsomedial (DMS) and ventrolateral striatum (VLS) to investigate whether A2A antagonists could act at this level. Infusion of SCH BT2 (5 microg/microl), a water-soluble analogue of SCH 58261, in VLS antagonized both tremor episodes (-68%) and jaw movements (-76%) elicited by tacrine (2.5 mg/kg ip), whereas SCH BT2 infusion in DMS was less effective in blocking jaw movements (-50%) and did not significantly affect the number of tremor episodes. Taken together, the results of this study indicate that A2A antagonists effectively reduce the magnitude of tremulous jaw movements induced in rats by acute tacrine, mainly by an action in VLS and suggest that A2A antagonists might be used as specific agents against parkinsonian tremor.
Simola
Nicola
N
Department of Toxicology and Centre of Excellence for Neurobiology of Dependence, University of Cagliari, 09124, Cagliari, Italy.
Fenu
Sandro
S
Baraldi
Pier G
PG
Tabrizi
Mojgan Aghazadeh
MA
Morelli
Micaela
M
D058917:Adenosine A2 Receptor Antagonists; D000818:Animals; D001522:Behavior, Animal; D003342:Corpus Striatum / Q000033:anatomy & histology / Q000187:drug effects*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007568:Jaw / Q000187:drug effects; D008297:Male; D009068:Movement / Q000187:drug effects; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000503:physiopathology*; D010879:Piperazines / Q000008:administration & dosage; D011743:Pyrimidines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D013619:Tacrine; D013997:Time Factors; D034402:Trema / Q000187:drug effects* / Q000502:physiology; D014230:Triazoles / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
C492656:2-furan-2-yl-7-3-(4-(4-(4-methylpiperazine-1-sulfonyl)phenylethyl)-7H-pyrazolo(4,3-e)(1,2,4)triazolo-(1,5-c)pyrimdin-5-ylamine); C098657:5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine; D058917:Adenosine A2 Receptor Antagonists; D010879:Piperazines; D011743:Pyrimidines; D014230:Triazoles; D013619:Tacrine