The Effects of Acute and Chronic Diphenhydramine and Cetirizine Use on Learning and Memory in Rats

Abstract

Antihistamines are one of the most widely used drug groups in various indications such as allergy, common cold and insomnia. Although these drugs are known to cause central nervous system side effects, their effects on cognitive functions such as learning and memory are not fully elucidated. We used in vivo hippocampal field potential recordings to assess the neuroplasticity changes caused by acute and chronic diphenhydramine and cetirizine treatment. Scopolamine is also used to assess the antimuscarinic effects of diphenhydramine. Furthermore, behavioral experiments were conducted to investigate the effect of cetirizine on cognitive performance. An REM sleep deprivation model was used to assess the effects of cetirizine in pathophysiological conditions. Acute use of diphenhydramine and cetirizine affected the potentiation phases of short-term plasticity while chronic treatment caused a tolerance to this effect. In long-term plasticity experiments, cetirizine blocked LTD in all groups and inhibited LTP in chronic treatment. Cetirizine prevented REM sleep deprivation-induced inhibition of LTP. Behavioral experiments with acute and chronic cetirizine treatment yielded no significant results. Our data showed that cetirizine has a significant effect in long-term plasticity that diphenhydramine failed to elicit. Therefore, cetirizine might be affecting the hippocampal circuitry independent of H1 receptor blockage through a previously unknown mechanism. Cetirizine use during sleep deprivation could be protective against cognitive dysfunction.