Roflumilast attenuates cognitive deficits in estrogen insufficient rats.

Behavioural Pharmacology
Ahsas Goyal, Debapriya Garabadu

Abstract

Estrogen replacement therapy including specific estrogen receptor alpha (ERα) agonist, 4,4',4″-(4-propyl-[1H] pyrazole-1,3,5-triyl) trisphenol (PPT), improves cognitive function in the females with estrogen insufficiency condition. It is well suggested that the cyclic nucleotides are considered as one of the downstream mediators to ERα receptor activity and they can be hypothesized as a potential target in the management of estrogen insufficiency condition. Roflumilast, a phosphodiesterase-4 inhibitor, increases the level of cyclic adenosine monophosphate (cAMP) in most of the tissues including the brain, and is reported to have procognitive activity in the experimental animals. Hence, the present study evaluated the therapeutic effect of roflumilast with or without PPT in rats with experimentally-induced estrogen insufficiency. Estrogen insufficiency was induced in female rats through bilateral ovariectomy on day-1 (D-1) of the experimental schedule. Roflumilast (0.3 and 1.0 mg/kg; p.o.) and PPT (333µg/kg; i.p.) attenuated ovariectomy-induced cognitive deficits in the rodents during behavioral tests. Roflumilast and PPT increased the cholinergic function and cAMP level in the rat hippocampus and prefrontal cortex. Further, ova...Continue Reading

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