Nicotinic acetylcholine receptor-mediated release of [ 3H]norepinephrine from developing and adult rat hippocampus: direct and indirect mechanisms

• Published in: Neuropharmacology Vol. 42; no. 5; pp. 653 - 661
• Main Authors: Leslie, F.M., Gallardo, K.A., Park, M.K.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01-04-2002; Elsevier
• Subjects: Animals; Animals, Newborn; Biological and medical sciences; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Dose-Response Relationship, Drug; Female; Fundamental and applied biological sciences. Psychology; GABA; Hippocampus - drug effects; Hippocampus - growth & development; Hippocampus - metabolism; Locus coeruleus; Male; Nicotine; Nicotine - pharmacology; Nicotinic Agonists - pharmacology; Nicotinic Antagonists - pharmacology; Norepinephrine - metabolism; Ontogeny; Pregnancy; Rats; Rats, Sprague-Dawley; Receptors, Nicotinic - physiology; Transmitter release; Tritium; Vertebrates: nervous system and sense organs; GABA; Transmitter release; Ontogeny; Locus coeruleus; Nicotine; Agonist; Rat; Rodentia; Central nervous system; Glutamate receptor; Catecholamine; In vitro; Young animal; Vertebrata; Alkaloid; Cholinergic receptor; Mammalia; Adult animal; Development; Norepinephrine; Muscarinic receptor; Antagonist; Mechanism of action; Gabaergic receptor A; Nicotinic receptor; Hippocampus; Brain (vertebrata)
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/S0028-3908(02)00019-9

The primary role of nicotinic acetylcholine receptors in adult and developing brain is to modulate neurotransmission. Using in vitro neurotransmitter release, we have examined mechanisms underlying nicotine-induced [
3H]norepinephrine release from developing and adult rat hippocampus. At birth, nicotine significantly stimulated hippocampal [
3H]norepinephrine release with a monotonic increase in maximal drug effect over the first ten postnatal days. No developmental changes in agonist or antagonist potency were observed. Comparison of synaptosomal and slice preparations, as well as examination of the effects of tetrodotoxin, indicated that at least two nicotinic acetylcholine receptor populations regulated [
3H]norepinephrine release from neonatal and adult hippocampus; one localized on noradrenergic terminals, the other on adjacent cells. To further characterize the indirect mechanism of nicotine action in the adult, we examined the effects of pharmacological blockade of various neurotransmitter systems that provide excitatory input to hippocampal noradrenergic terminals. Whereas glutamate and muscarinic receptor blockade was ineffective, the GABA-A receptor antagonists, bicuculline and picrotoxin, inhibited the indirect component of nicotine-mediated [
3H]norepinephrine release. Furthermore, pentobarbital, an allosteric effector at GABA-A receptors, potentiated the effect of submaximal concentrations of nicotine. These findings are consistent with the hypothesis that nicotine-induced GABA release serves as an additional stimulus for [
3H]norepinephrine secretion within rat hippocampus.