Blockade of adenosine A(2A) receptors reverses short-term social memory impairments in spontaneously hypertensive rats.

摘要

Spontaneously hypertensive rats (SHR) exhibit impairment across several cognitive domains such as attention, short-term memory and spatial reference memory. These cognitive deficits have been variously attributed to disrupted dopaminergic, cholinergic and adenosinergic neurotransmitter function. However, social memory in SHR has not been investigated. In the present study, we therefore evaluated whether SHR exhibit altered short-term social memory abilities compared to normotensive Wistar rats (WIS) through two experimental paradigms (social recognition and habituation-dishabituation tests). We also compared the performance of SHR and WIS rats in the object recognition test. SHR exhibited significantly impaired performance in both models of social memory, but not in the object recognition test, demonstrating a selective deficit in the ability to recognize a juvenile rat after a short period of time. The administration of acute doses of the non-selective adenosine receptor antagonist caffeine (3.0 or 10.0mg/kg, i.p.) and the adenosine A(2A) receptor antagonist 4-(2-[7-amino-2-{2-furyl}{1,2,4}triazolo-{2,3-a}{1,3,5}triazin-5-yl-amino] ethyl) phenol (ZM241385, 0.5 or 1.0mg/kg, i.p.) but not the adenosine A(1) receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 1.0 or 3.0mg/kg, i.p.) reversed this social memory impairment in SHR, but these treatments did not alter the hypertension state. These results demonstrate an impairment of short-term social memory in SHR and the involvement of the adenosine A(2A) receptors in this alteration.