Activation of adenosine A(1) receptors alters behavioral and biochemical parameters in hyperthyroid rats.
Adenosine acting on A(1) receptors has been related with neuroprotective and neuromodulatory actions, protection against oxidative stress and decrease of anxiety and nociceptive signaling. Previous studies demonstrated an inhibition of the enzymes that hydrolyze ATP to adenosine in the rat central nervous system after hyperthyroidism induction. Manifestations of hyperthyroidism include increased anxiety, nervousness, high O(2) consumption and physical hyperactivity. Here, we investigated the effects of administration of a specific agonist of adenosine A(1) receptor (N(6)-cyclopentyladenosine; CPA) on nociception, anxiety, exploratory response, locomotion and brain oxidative stress of hyperthyroid rats. Hyperthyroidism was induced by daily intraperitoneal injections of l-thyroxine (T4) for 14 days. Nociception was assessed with a tail-flick apparatus and exploratory behavior, locomotion and anxiety were analyzed by open-field and plus-maze tests. We verified the total antioxidant reactivity (TAR), lipid peroxide levels by the thiobarbituric acid reactive species (TBARS) reaction and the free radicals content by the DCF test. Our results demonstrated that CPA reverted the hyperalgesia induced by hyperthyroidism and decreased the exploratory behavior, locomotion and anxiety in hyperthyroid rats. Furthermore, CPA decreased lipid peroxidation in hippocampus and cerebral cortex of control rats and in cerebral cortex of hyperthyroid rats. CPA also increased the total antioxidant reactivity in hippocampus and cerebral cortex of control and hyperthyroid rats, but the production of free radicals verified by the DCF test was changed only in cerebral cortex. These results suggest that some of the hyperthyroidism effects are subjected to regulation by adenosine A(1) receptor, demonstrating the involvement of the adenosinergic system in this pathology.
Bruno
Alessandra Nejar
AN
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Avenida Ramiro Barcellos, 2600-ANEXO, 90035-003 Porto Alegre, RS, Brazil.
Fontella
Fernanda Urruth
FU
Bonan
Carla Denise
CD
Barreto-Chaves
Maria Luiza M
ML
Dalmaz
Carla
C
Sarkis
João José Freitas
JJ
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D058907:Adenosine A1 Receptor Agonists; D000704:Analysis of Variance; D000818:Animals; D001007:Anxiety / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D005106:Exploratory Behavior / Q000187:drug effects* / Q000502:physiology; D006980:Hyperthyroidism / Q000378:metabolism*; D008297:Male; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D017288:Pain Threshold / Q000187:drug effects* / Q000502:physiology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D043682:Receptor, Adenosine A1 / Q000378:metabolism; D018709:Statistics, Nonparametric; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D058907:Adenosine A1 Receptor Agonists; D043682:Receptor, Adenosine A1; D017392:Thiobarbituric Acid Reactive Substances; C048599:N(6)-cyclopentyladenosine; D000241:Adenosine