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 no. 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 no. of both tremor episodes (-35%) and jaw movements (-50%), induced in rats by tacrine (2.5 mg/kg i.p.). 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 g/L), a water-sol. analog of SCH 58261, in VLS antagonized both tremor episodes (-68%) and jaw movements (-76%) elicited by tacrine (2.5 mg/kg i.p.), whereas SCH BT2 infusion in DMS was less effective in blocking jaw movements (-50%) and did not significantly affect the no. 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.
Blockade of adenosine A(2A) receptors antagonizes parkinsonian tremor in the rat tacrine model by an action on specific striatal regions
BARALDI, Pier Giovanni;AGHAZADEH TABRIZI, Mojgan;
2004
Abstract
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 no. 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 no. of both tremor episodes (-35%) and jaw movements (-50%), induced in rats by tacrine (2.5 mg/kg i.p.). 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 g/L), a water-sol. analog of SCH 58261, in VLS antagonized both tremor episodes (-68%) and jaw movements (-76%) elicited by tacrine (2.5 mg/kg i.p.), whereas SCH BT2 infusion in DMS was less effective in blocking jaw movements (-50%) and did not significantly affect the no. 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.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.