Pentoxifylline improves learning and memory in glutamate-lesioned rats.
The present work shows the effects of pentoxifylline (ptx), on learning and memory in rats with hippocampal lesions induced by glutamate (glu). Immediately after stereotaxic procedures and in the absence or presence of glu lesions, animals were treated with ptx (50, 100, or 200 mg/kg, IP) for 6 days. Twenty-four hours after the last injection, behavior and memory tests were performed, animals were sacrificed, and hippocampi dissected for cAMP determination or histopathological studies. Results from the T-maze task showed a less learning ability in the glu-lesioned group compared to other ones. Ptx alone or associated with glu significantly improved memory acquisition, but not memory consolidation compared to glu-lesioned rats. Except for the increased locomotor activity observed in the ptx100+glu-treated group compared to saline, no other difference was detected in the open-field test. A significant impairment in avoidance performance was observed in glu-lesioned group as compared to saline or to other groups in the short as well as in the late phase of memory. All groups showed an improved water-maze performance over time with similar performances on the final day of acquisition. The impairment in memory retention observed in glu-lesioned rats was reversed by the pretreatment with ptx200. Glu induced hippocampal lesion and reduced cAMP levels. Both effects were blocked by ptx, suggesting that its action may be the result of increased cAMP levels and/or inhibition of adenosine A1 receptors.
Cunha
G M
GM
Department of Physiology and Pharmacology, Laboratory of Neuropharmacology, Federal University of Ceara, Brazil.
Bezerra
P J
PJ
Saldanha
M D
MD
Cavalcante
M C
MC
De Brun
V M
VM
Viana
G S
GS
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D018698:Glutamic Acid / Q000633:toxicity*; D006624:Hippocampus / Q000187:drug effects; D007858:Learning / Q000187:drug effects*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D010431:Pentoxifylline / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017470:Receptors, Glutamate / Q000187:drug effects*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects
D010726:Phosphodiesterase Inhibitors; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D000242:Cyclic AMP; D010431:Pentoxifylline