The Effect of Adenosine Signaling on Memory Impairment Induced by Pentylenetetrazole in Zebrafish

Epilepsy is characterized by the manifestation of spontaneous and recurrent seizures. The high prevalence of comorbidities associated with epilepsy, such as cognitive dysfunction, affects the patients quality of life. Adenosine signaling modulation might be an effective alternative to control seizures and epilepsy-associated comorbidities. This study aimed to verify the role of adenosine modulation on the seizure development and cognitive impairment induced by pentylenetetrazole (PTZ) in zebrafish. At first, animals were submitted to a training session in the inhibitory avoidance test and, after 10 min, they received an intraperitoneal injection of valproate, adenosine A(1) receptor agonist cyclopentyladenosine (CPA), adenosine A(1) receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), adenosine A(2A) receptor antagonist ZM 241385, adenosine deaminase inhibitor erythro-9-(2-hydroxy-3-nony1)-adenine hydrochloride (EHNA) or the nucleoside transporter inhibitor dipyridamole. Thirty min after the intraperitoneal injection, the animals were exposed to 7.5 mM PTZ for 10 min, where they were evaluated for latency to reach the seizure stages (I, II, and III). Finally, 24 h after the training session, the animals were submitted to the inhibitory avoidance test to verify their cognitive performance during the test session. Valproate, CPA, and EHNA showed antiseizure effects and prevented the memory impairment induced by PTZ exposure. DPCPX, ZM 241385, and dipyridamole pretreatments caused no changes in seizure development; however, these drugs prevented memory impairment without altering locomotion. Our results reinforce the antiseizure effects of adenosine signaling and support the idea that the involvement of adenosine in memory processes may be a target for preventive strategies against cognitive impairment associated with epilepsy.

Automated summary

Epilepsy is a condition characterized by spontaneous and recurring seizures. This study investigated the role of adenosine modulation in controlling seizures and cognitive impairment in zebrafish. The results showed that certain drugs like valproate, CPA, and EHNA had anti-seizure effects and prevented memory impairments induced by PTZ exposure. Other drugs like DPCPX, ZM 241385, and dipyridamole prevented memory impairments without affecting seizure development. These findings highlight the potential of adenosine signaling as a target for preventing cognitive impairments associated with epilepsy.