TY - JOUR
T1 - Effects of nicotinic antagonists on working memory performance in young rhesus monkeys
AU - Upright, Nicholas A.
AU - Baxter, Mark G.
N1 - Publisher Copyright:
© 2021 Elsevier Inc.
PY - 2021/10
Y1 - 2021/10
N2 - Acetylcholine plays a pivotal neuromodulatory role in the brain, influencing neuronal activity and cognitive function. Nicotinic receptors, particularly α7 and α4β2 receptors, modulate firing of dorsolateral prefrontal (dlPFC) excitatory networks that underlie successful working memory function. Minimal work however has been done examining working memory following systemic blockade of nicotinic receptor systems in nonhuman primates, limiting the ability to explore interactions of other neuromodulatory influences with working memory impairment caused by nicotinic antagonism. In this study, we investigated working memory performance after administering three nicotinic antagonists, mecamylamine, methyllycaconitine, and dihydro-β-erythroidine, in rhesus macaques tested in a spatial delayed response task. Surprisingly, we found that no nicotinic antagonist significantly impaired delayed response performance compared to vehicle. In contrast, the muscarinic antagonist scopolamine reliably impaired delayed response performance in all monkeys tested. These findings suggest there are some limitations on using systemic nicotinic antagonists to probe the involvement of nicotinic receptors in aspects of dlPFC-dependent working memory function, necessitating alternative strategies to understand the role of this system in cognitive deficits seen in aging and neurodegenerative disease.
AB - Acetylcholine plays a pivotal neuromodulatory role in the brain, influencing neuronal activity and cognitive function. Nicotinic receptors, particularly α7 and α4β2 receptors, modulate firing of dorsolateral prefrontal (dlPFC) excitatory networks that underlie successful working memory function. Minimal work however has been done examining working memory following systemic blockade of nicotinic receptor systems in nonhuman primates, limiting the ability to explore interactions of other neuromodulatory influences with working memory impairment caused by nicotinic antagonism. In this study, we investigated working memory performance after administering three nicotinic antagonists, mecamylamine, methyllycaconitine, and dihydro-β-erythroidine, in rhesus macaques tested in a spatial delayed response task. Surprisingly, we found that no nicotinic antagonist significantly impaired delayed response performance compared to vehicle. In contrast, the muscarinic antagonist scopolamine reliably impaired delayed response performance in all monkeys tested. These findings suggest there are some limitations on using systemic nicotinic antagonists to probe the involvement of nicotinic receptors in aspects of dlPFC-dependent working memory function, necessitating alternative strategies to understand the role of this system in cognitive deficits seen in aging and neurodegenerative disease.
KW - Monkey
KW - Nicotinic
KW - Prefrontal
KW - Working memory
UR - http://www.scopus.com/inward/record.url?scp=85113690010&partnerID=8YFLogxK
U2 - 10.1016/j.nlm.2021.107505
DO - 10.1016/j.nlm.2021.107505
M3 - Article
C2 - 34425219
AN - SCOPUS:85113690010
SN - 1074-7427
VL - 184
JO - Neurobiology of Learning and Memory
JF - Neurobiology of Learning and Memory
M1 - 107505
ER -