Agmatine reduces balance deficits in a rat model of third trimester binge-like ethanol exposure

Abstract

This study examined the effects of binge-like ethanol (ETOH) exposure in neonatal rats on a cerebellar-mediated balance task, and the ability of agmatine, an n-methyl-d-aspartate receptor (NMDAR) modulator, to reverse such effects. Five neonatal treatments groups were used, including ETOH (6.0 g/kg/day), AG (20 mg/kg), ETOH plus AG (6.0 g/kg/day and 20 mg/kg), a maltose control, and a non-treated control. Ethanol was administered via oral intubation twice daily for eight days, (AG was administered with the last ETOH intubation only). Two exposure periods were used; PND 1-8 or PND 8-15. On PND 31-33, balance performance on a single dowel was tested. Treatment with AG during withdrawal in ETOH exposed animals improved performance relative to ETOH alone among the PND 1-8 exposure period. ETOH exposure during the 2 nd postnatal week did not impair balance. These findings provide further support that exposure to ETOH during critical developmental periods can impair performance on a cerebellar-dependent balance task. Of perhaps greater significance, co-administration of agmatine reduced these deficits suggesting that NMDA modulation via polyamine blockade may provide a novel approach to attenuating damage associated with binge-like ETOH consumption.

The arginine metabolite agmatine protects mitochondrial function and confers resistance to cellular apoptosis

“…Suppression of apoptosis in the early mesangiolytic phase of this model would account for the beneficial effect of agmatine on the GFR. Agmatine is beneficial in several other experimental models including hypoxia (17,30), ischemia-reperfusion (26,35,36,38,65,72), N-methyl-D-aspartic acid or glucocorticoid damage (41,69,76), spinal cord and nerve injury (8,23,37,74), and diabetes (39). We observed selective inhibition of inducible NO synthase by the aldehyde metabolite of agmatine and beneficial effects of agmatine administration in the LPS model of endotoxic shock (60).…”

Age and Gender Differences in Response to Neonatal Ethanol Withdrawal and Polyamine Challenge in Organotypic Hippocampal Cultures

“…In vivo exposure to ETOH during the first postnatal week results in a variety of behavioral deficits while exposure during the second postnatal week has far less significant behavioral consequences (Gilbertson and Barron, 2005). Furthermore, these deficits are diminished with agents that either block the polyamine site or reduce polyamine synthesis (Lewis et al, 2007).…”

Fetal Alcohol Spectrum Disorders and Neuroimmune Changes

“…Functional development of neurons is inhibited as evidenced by impaired migration, stunted development of dendrites, reduction in the number of synapses, and impaired electrophysiological activity (Allam et al, 2013; Jiang, Kumada, Cameron, & Komuro, 2008; Kane et al, 2011; Servais et al, 2007; Smith & Davies, 1990; Valenzuela, Lindquist, & Zamudio-Bulcock, 2010). These defects contribute to the deficits in motor coordination and classical conditioning commonly observed in rodent models of FASD (Brown, Calizo, & Stanton, 2008; Goodlett, Thomas, & West, 1991; Idrus, McGough, Riley, & Thomas, 2011; Klintsova et al, 1998; Lewis, Wellmann, & Barron, 2007; Murawski, Jablonski, Brown, & Stanton, 2013; Wagner, Klintsova, Greenough, & Goodlett, 2013). …”

“…Ethanol-induced cerebellar pathology underlies deficits in classical eyeblink conditioning tasks (Brown et al, 2008; Murawski et al, 2013; Wagner et al, 2013). The cerebellum is centrally involved in motor function and ethanol impairs balance and coordination in rodents exposed to ethanol during early postnatal development (Goodlett et al, 1991; Idrus et al, 2011; Klintsova et al, 1998; Lewis et al, 2007). …”