Comparison of Galantamine and Donepezil for Effects on Nerve Growth Factor, Cholinergic Markers, and Memory Performance in Aged Rats

Abstract

This study was designed to determine 1) whether repeated exposures to the acetylcholinesterase inhibitors (AChEIs) galantamine (GAL) or donepezil (DON) resulted in positive effects on nerve growth factor (NGF) and its receptors, cholinergic proteins, and cognitive function in the aged rat, and 2) whether GAL had any advantages over DON given its allosteric potentiating ligand (APL) activity at nicotinic acetylcholine receptors. Behavioral tests (i.e., water maze and light/dark box) were conducted in aged Fisher 344 rats during 15 days of repeated (subcutaneous) exposure to either GAL (3.0 or 6.0 mg/kg/day) or DON (0.375 or 0.75 mg/kg/day). Forty-eight hours after the last drug injection, cholinergic receptors were measured by The prevalence of age-related cognitive disorders such as Alzheimer's disease (AD) is predicted to reach epidemic proportions in developed countries by the middle of this century (Brookmeyer et al., 1998). This result of the growing geriatric population clearly provides the impetus for the development of more effective (dementia-related) therapeutic agents. Current therapy, acetylcholinesterase inhibitors (AChEIs) such as donepezil (DON) or galantamine (GAL), is supported by prospective clinical trial evidence of cognitive benefits in patients with mild to moderate AD (Winblad et al., 2001;

Combination of Rimonabant and Donepezil Prolongs Spatial Memory Duration

“…Several studies have reported that donepezil has no effect or impairs performance in healthy rodents, but that it reverses deficits induced pharmacologically or by brain lesions (Rupniak et al, 1997;Poorheidari et al, 1998;Higgins et al, 2002;Bontempi et al, 2003;Takahashi et al, 2005;Yamada et al, 2005). Donepezil also improves performance of aged rats and mice in the Morris water maze (Hernandez et al, 2006), as well as in spontaneous alternation in the T-maze and in a delayed nonmatch to place task in the radial-arm maze (Bontempi et al, 2003). Additionally, there are reports of donepezil reversing memory deficits induced pharmacologically or by lesions in the radial-arm maze (Braida et al, 1996;Cheng et al, 1996;Cheng and Tang, 1998;Ogura et al, 2000).…”

“…Donepezil reversed scopolamineinduced impairments in spontaneous alternation in the Tmaze in young and aged mice as well as in a delayed nonmatch to place task in the radial-arm maze (Bontempi et al, 2003). Repeated administration of donepezil improved the memory performance of aged rats in the Morris water maze (Hernandez et al, 2006) and reversed amyloid b-induced memory impairments in a delayed matching to position paradigm (Yamada et al, 2005). Additionally, this agent reversed learning impairments in the passive avoidance task induced by lesions in the nucleus basalis magnocellularis and scopolamine (Cheng et al, 1996;Ogura et al, 2000), and ethylcholine mustard aziridinium ion (AF64A) (Cheng and Tang, 1998) induced impairments in eight-arm radial maze tasks (Braida et al, 1996).…”

Discrimination performance in aging is vulnerable to interference and dissociable from spatial memory

“…Prior studies in aged rats have found that chronic treatment with donepezil did not affect spatial working memory (Barnes et al 2000), but improved spatial reference memory (Hernandez et al 2006). Similarly, older adults diagnosed with mild cognitive impairment who were treated with galantamine showed improvements in delayed recall, but not measures of attention, working memory, or susceptibility to interference (Grön et al 2006).…”

Galantamine and donepezil attenuate pharmacologically induced deficits in prepulse inhibition in rats

“…Galantamine was tested at doses of 0.3, 1.0, and 3.0 mg/kg while donepezil doses were 0.5, 1.0, and 2.0 mg/kg. These doses were based on data obtained in rats in which brain levels of the compounds and the degree of acetylcholinesterase inhibition were compared across a dose and time (Geerts et al, 2005) as well as recent neuropharmacological and behavioral studies in our laboratory (Hernandez et al, 2006).…”