Low-dose nicotine facilitates spatial memory in ApoE-knockout mice in the radial arm maze

Abstract

Here, we investigated the effects of nicotine on spatial memory in ApoE-knockout (ApoE-KO) and wild-type (WT) mice in a radial arm maze. Training occurred on three consecutive days and the test was performed on day 4, with one trial per day. Then on day 4, animals were administered nicotine (0.1, 0.25, 0.5, and 1.0 mg/kg) or the antagonist of nicotinic receptors (nAChRs) mecamylamine (MEC 2 mg/kg) alone or together with 0.1 mg/kg nicotine. The number of errors in the first eight choices was recorded. The results were that 0.1 mg/kg nicotine decreased errors in ApoE-KO mice, while 0.1 and 0.25 mg/kg nicotine reduced errors in WT mice, indicating that lower doses of nicotine elicit a memory improvement. In contrast, 1.0 mg/kg nicotine increased errors in WT mice, but not in ApoE-KO mice. MEC alone had no noticeable effect on errors in either strain of mice. However, co-administration of 0.1 mg/kg nicotine and MEC increased errors and reduced the effects of nicotine in WT mice, but not in ApoE-KO mice. Our study found a biphasic effect of nicotine in WT mice: it improves spatial memory at lower doses and impairs it at a higher dose. In ApoE-KO mice, nicotine improves memory at a low dose and has no effect at a higher dose, suggesting that the ApoE deficiency may influence the efficacy of nicotine. Moreover, a reversal of nicotinic effects with MEC was seen in WT mice, indicating the likelihood of the involvement of nAChRs in the spatial-memory response to nicotine.

Nicotine attenuates the effect of HIV-1 proteins on the neural circuits of working and contextual memories

“…Stimulation of the cholinergic system by nicotinic acetylcholine receptor (nAChR) agonists protects against glutamate-mediated neurotoxicity and leads to subsequent cognitive improvement in rodent models of neurodegenerative disorders [ 20 ]. A low dose of nicotine enhances cognitive performance by attenuating the impairment of cholinergic neurotransmission [ 21 , 22 ]. Experimental treatment of neurodegenerative disorders shows that nicotine mediates neuroprotection against NMDA-mediated excitotoxicity in the neurons by calcium-dependent mechanisms via neuronal α4β2- and α7-containing nAChRs [ 23 – 26 ].…”

Potential Use of Nicotinic Receptor Agonists for the Treatment of Chemotherapy-Induced Cognitive Deficits

“…Spatial memory of the radial arm maze and Morris water maze can be improved in unimpaired animals by the administration of nicotine and this effect can be blocked by the administration of the nAChR antagonist mecamylamine [167][168][169], indicating that the performance enhancing effects of nicotine are nAChR dependent. Additionally, nicotine improves performance in several models of impaired spatial memory.…”

“…Additionally, nicotine prevents the adverse effects of stress and Ab infusion on performance in the submerged radial arm maze [172,173]. In the Morris water maze, nicotine administration attenuates spatial learning deficits in lead-exposed animals [174], reverses AF64A-induced and sodium metavanadate-induced deficits in Morris water maze performance and improves Morris water maze performance in Apo-E knockout mice [169,175,176].…”

Nicotine promotes the utility of short-term memory during visual search in macaque monkeys

“…Nicotine administration is known to improve a variety of cognitive functions (Rezvani and Levin 2001). In particular, the effect on WM has been reported in rodents (Rushforth et al 2011), pigeons (Kangas and Branch 2012), monkeys (Buccafusco et al 1999;Buccafusco and Terry 2004), and humans (Heishman et al 2010;Kangas and Branch 2012;Levin et al 1996;Spinelli et al 2006;Sultana et al 2013;Upright and Baxter 2021). Katner et al (2004) examined the effects of nicotine in monkeys trained on a variety of WM tasks and found that performance improved regardless of memory domain, with more difficult conditions showing a greater effect.…”