Agmatine Improves Olfactory and Cognitive Deficits in Spontaneously Hypertensive Rats (SHR): An Animal Model of Attention Deficit Hyperactivity Disorder (ADHD)

Attention Deficit Hyperactivity Disorder (ADHD) is a highly prevalent and disabling disorder that frequently persists into adulthood. Many patients are considered nonresponders to typical pharmacological treatments due to insufficient symptoms' reduction or the inability to tolerate the side effects of these medications. Agmatine is an endogenous neuromodulator with emotional- and cognitive-enhancing properties that arises as a promising agent to manage several Central Nervous System disorders. Here, we investigated the effects of chronic treatment with agmatine on behavioral impairments exhibited by adult Spontaneously Hypertensive Rats (SHR), an animal model for the study of ADHD. Adult male Wistar and SHR (3-4 months old) received intraperitoneal (i.p.) treatment with saline (NaCl0.9%) or agmatine (30 mg/ kg/day) during 20 consecutive days and were evaluated in a battery of behavioral tasks. Agmatine treatment improved olfactory and recognition memory impairments of SHR evaluated in the olfactory discrimination, object recognition, and social recognition memory tasks. In addition, agmatine administration improved the cognitive flexibility in the water maze test. Agmatine did not alter SHR' s locomotor activity and hedoniclike behaviors observed in the open-field and splash tests, respectively. No changes were observed in SHR' s systolic blood pressure following agmatine treatment. This study provides the first evidence that agmatine improves olfactory and cognitive impairments observed in an animal model of ADHD.