Developmental regulation of nicotinic acetylcholine receptors within midbrain dopamine neurons

• Published in: Neuroscience Vol. 144; no. 4; pp. 1347 - 1360
• Main Authors: Azam, L, Chen, Y, Leslie, F.M
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 23-02-2007; Elsevier
• Subjects: adolescent; Aging - physiology; Animals; Animals, Newborn; Biological and medical sciences; Corpus Striatum - growth & development; Corpus Striatum - metabolism; Dopamine - metabolism; Dopamine - secretion; Female; fetal; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Developmental; Male; maternal smoking; Neurology; Neurons - drug effects; Neurons - metabolism; nicotine; Nicotine - pharmacology; Nicotinic Agonists - pharmacology; Pregnancy; Prenatal Exposure Delayed Effects - metabolism; Prenatal Exposure Delayed Effects - physiopathology; Presynaptic Terminals - drug effects; Presynaptic Terminals - metabolism; Presynaptic Terminals - secretion; Protein Subunits - genetics; Protein Subunits - metabolism; Rats; Rats, Sprague-Dawley; Receptors, Nicotinic - genetics; Receptors, Nicotinic - metabolism; RNA, Messenger - metabolism; sex; Sex Characteristics; striatum; Substantia Nigra - growth & development; Substantia Nigra - metabolism; Up-Regulation - physiology; Ventral Tegmental Area - growth & development; Ventral Tegmental Area - metabolism; Vertebrates: nervous system and sense organs; RT; room temperature; VTA; 35S-UTP; gestational day; G; phosphate buffer; Genius buffer; fetal; P; striatum; nAChR; postnatal day; standard saline citrate; maternal smoking; GB; nicotinic acetylcholine receptor; nicotine; substantia nigra; SSC; Dig; 35S-uridine triphosphate; digoxygenin; sex; NIC; SNc; dihydroxyphenylethylamine dopamine; tyrosine hydroxylase; α-BTX; PB; TH; ventral tegmental area; α-bungarotoxin; adolescent; DA; Human; Cholinergic neuron; Dopamine receptor; Central nervous system; Sex; Midbrain; Basal ganglion; Corpus striatum; Encephalon; Cholinergic receptor; Adolescent; Development; Fetus; Nicotinic receptor; Nicotine
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2006.11.011

Abstract We have combined anatomical and functional methodologies to provide a comprehensive analysis of the properties of nicotinic acetylcholine receptors (nAChRs) on developing dopamine (DA) neurons of Sprague–Dawley rats. Double-labeling in situ hybridization was used to examine the expression of nAChR subunit mRNAs within developing midbrain DA neurons. As brain maturation progressed there was a change in the pattern of subunit mRNA expression within DA neurons, such that α3 and α4 subunits declined and α6 mRNA increased. Although there were strong similarities in subunit mRNA expression in substantia nigra (SNc) and ventral tegmental area (VTA), there was higher expression of α4 mRNA in SNc than VTA at gestational day (G) 15, and of α5, α6 and β3 mRNAs during postnatal development. Using a superfusion neurotransmitter release paradigm to functionally characterize nicotine-stimulated release of [3 H]DA from striatal slices, the properties of the nAChRs on DA terminals were also found to change with age. Functional nAChRs were detected on striatal terminals at G18. There was a decrease in maximal release in the first postnatal week, followed by an increase in nicotine efficacy and potency during the second and third postnatal weeks. In the transition from adolescence (postnatal days (P) 30 and 40) to adulthood, there was a complex pattern of functional maturation of nAChRs in ventral, but not dorsal, striatum. In males, but not females, there were significant changes in both nicotine potency and efficacy during this developmental period. These findings suggest that nAChRs may play critical functional roles throughout DA neuronal maturation.