Premium
Caffeine and an adenosine A 2A receptor antagonist prevent memory impairment and synaptotoxicity in adult rats triggered by a convulsive episode in early life
Author(s) -
Cognato Giana P.,
Agostinho Paula M.,
Hockemeyer Jörg,
Müller Christa E.,
Souza Diogo O.,
Cunha Rodrigo A.
Publication year - 2010
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2009.06465.x
Subject(s) - kainate receptor , adenosine receptor , caffeine , adenosine receptor antagonist , medicine , nmda receptor , endocrinology , glutamate receptor , adenosine , hippocampus , neuroscience , ampa receptor , psychology , pharmacology , receptor , agonist
Seizures early in life cause long‐term behavioral modifications, namely long‐term memory deficits in experimental animals. Since caffeine and adenosine A 2A receptor (A 2A R) antagonists prevent memory deficits in adult animals, we now investigated if they also prevented the long‐term memory deficits caused by a convulsive period early in life. Administration of kainate (KA, 2 mg/kg) to 7‐days‐old (P7) rats caused a single period of self‐extinguishable convulsions which lead to a poorer memory performance in the Y‐maze only when rats were older than 90 days, without modification of locomotion or anxiety‐like behavior in the elevated‐plus maze. In accordance with the relationship between synaptotoxicity and memory dysfunction, the hippocampus of these adult rats treated with kainate at P7 displayed a lower density of synaptic proteins such as SNAP‐25 and syntaxin (but not synaptophysin), as well as vesicular glutamate transporters type 1 (but not vesicular GABA transporters), with no changes in PSD‐95, NMDA receptor subunits (NR1, NR2A, NR2B) or α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionate receptor subunits (GluR1, GluR2) compared with controls. Caffeine (1 g/L) or the A 2A R antagonist, KW6002 (3 mg/kg) applied in the drinking water from P21 onwards, prevented these memory deficits in P90 rats treated with KA at P7, as well as the accompanying synaptotoxicity. These results show that a single convulsive episode in early life causes a delayed memory deficit in adulthood accompanied by a glutamatergic synaptotoxicity that was prevented by caffeine or adenosine A 2A R antagonists.