Inhibitory effect of lithium on nucleotide hydrolysis and acetylcholinesterase activity in zebrafish ( Danio rerio) brain

Abstract

Lithium has been used as an effective antimanic drug in humans and it is well known for its effects on neuropsychiatric disorders and neuronal communication. ATP and adenosine are important signaling molecules, and most nerves release ATP as a fast co-transmitter together with classical neurotransmitters such as acetylcholine. In this study, we evaluated the in vitro and in vivo effects of lithium on acetylcholinesterase and ectonucleotidase activities in zebrafish brain. There was a significant inhibition of ADP hydrolysis after in vivo exposure to lithium at 5 and 10 mg/l (27.6% and 29% inhibition, respectively), whereas an inhibitory effect was observed for AMP hydrolysis only at 10 mg/l (30%). Lithium treatment in vivo also significantly decreased the acetylcholinesterase activity at 10 mg/l (21.9%). The mRNA transcript levels of the genes encoding for these enzymes were unchanged after exposure to 5 and 10 mg/l lithium chloride. In order to directly evaluate the action of lithium on enzyme activities, we tested the in vitro effect of lithium at concentrations ranging from 1 to 1000 μM. There were no significant changes in zebrafish brain ectonucleotidase and acetylcholinesterase activities at all concentrations tested in vitro. Our findings show that lithium treatment can alter ectonucleotidase and acetylcholinesterase activities, which may regulate extracellular nucleotide, nucleoside, and acetylcholine levels. These data suggest that cholinergic and purinergic signaling may be targets of the pharmacological effects induced by this compound.