title: Age-related changes in nicotine response of cholinergic and non-cholinergic laterodorsal tegmental neurons: implications for the heightened adolescent susceptibility to nicotine addiction.
abstract: The younger an individual starts smoking, the greater the likelihood that addiction to nicotine will develop, suggesting that neurobiological responses vary across age to the addictive component of cigarettes. Cholinergic neurons of the laterodorsal tegmental nucleus (LDT) are importantly involved in the development of addiction, however, the effects of nicotine on LDT neuronal excitability across ontogeny are unknown. Nicotinic effects on LDT cells across different age groups were examined using calcium imaging and whole-cell patch clamping. Within the youngest age group (P7-P15), nicotine induced larger intracellular calcium transients and inward currents. Nicotine induced a greater number of excitatory synaptic currents in the youngest animals, whereas larger amplitude inhibitory synaptic events were induced in cells from the oldest animals (P15-P34). Nicotine increased neuronal firing of cholinergic cells to a greater degree in younger animals, possibly linked to development associated differences found in nicotinic effects on action potential shape and afterhyperpolarization. We conclude that in addition to age-associated alterations of several properties expected to affect resting cell excitability, parameters affecting cell excitability are altered by nicotine differentially across ontogeny. Taken together, our data suggest that nicotine induces a larger excitatory response in cholinergic LDT neurons from the youngest animals, which could result in a greater excitatory output from these cells to target regions involved in development of addiction. Such output would be expected to be promotive of addiction; therefore, ontogenetic differences in nicotine-mediated increases in the excitability of the LDT could contribute to the differential susceptibility to nicotine addiction seen across age.
authors.affiliation: University of Copenhagen, Department of Drug Design and Pharmacology, Faculty of Health Sciences, Universitetsparken 2, Copenhagen 2100, Denmark.
authors.forename: Mark H
authors.initials: MH
authors.lastname: Christensen
authors.affiliation: Department of Physiology, New York Medical College, Valhalla, NY 10595, USA.
authors.forename: Masaru
authors.initials: M
authors.lastname: Ishibashi
authors.affiliation: University of Copenhagen, Department of Drug Design and Pharmacology, Faculty of Health Sciences, Universitetsparken 2, Copenhagen 2100, Denmark.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Nielsen
authors.affiliation: Department of Physiology, New York Medical College, Valhalla, NY 10595, USA.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Leonard
authors.affiliation: University of Copenhagen, Department of Drug Design and Pharmacology, Faculty of Health Sciences, Universitetsparken 2, Copenhagen 2100, Denmark. Electronic address: kak1@sund.ku.dk.
authors.forename: Kristi A
authors.initials: KA
authors.lastname: Kohlmeier
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000375:Aging / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002412:Cations / Q000378:metabolism; D059329:Cholinergic Neurons / Q000187:drug effects* / Q000502:physiology; D017097:Electric Impedance; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D055369:Miniature Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D013681:Tegmentum Mesencephali / Q000187:drug effects* / Q000254:growth & development* / Q000502:physiology; D046509:Tissue Culture Techniques
chemical_list: D002412:Cations; D018722:Nicotinic Agonists; D009538:Nicotine; D002118:Calcium
keywords: Electrophysiology; LDT; Mouse; REM sleep