Cholinergic transmission during nicotine withdrawal is influenced by age and pre-exposure to nicotine: Implications for teenage smokingDevelopmental Neuroscience (2014)
AbstractAdolescence is a unique period of development characterized by enhanced tobacco use and long-term vulnerability to neurochemical changes produced by adolescent nicotine exposure. In order to understand the underlying mechanisms that contribute to developmental differences in tobacco use, this study compared changes in cholinergic transmission produced by exposure to nicotine and withdrawal from nicotine in rats of different ages, some of which had exposure to nicotine as adolescents. The first study compared extracellular levels of acetylcholine (ACh) in the nucleus accumbens (NAcc) during nicotine withdrawal in adolescent, adult and adult rats that were exposed to nicotine during adolescence. Adolescent (PND 28-42) and adult rats (PND 60-74) were prepared with osmotic pumps that delivered nicotine for 14 days (4.7 mg/kg/day adolescents; 3.2 mg/kg/day adults). Another group of adults was exposed to nicotine during adolescence and then again in adulthood (pre-exposed adults) using similar methods. Following 13 days of nicotine exposure, rats were implanted with microdialysis probes in the NAcc. The following day, dialysis samples were collected during baseline and following systemic administration of the nicotinic-receptor antagonist mecamylamine (1.5 mg/kg and 3.0 mg/kg, IP) to precipitate withdrawal. A second study examined various metabolic differences in cholinergic transmission in separate groups of adolescent, adult and pre-exposed adult rats. The same treatment procedures were used as the first study. Following 14 days of nicotine exposure, the NAcc was dissected and acetylcholinesterase (AChE) activity was compared across experimental groups. In order to examine potential group differences in nicotine metabolism, blood plasma levels of cotinine (a nicotine metabolite) were also compared following 14 days of nicotine exposure. The results from the first study revealed that baseline ACh was highest in the NAcc of adolescents versus both groups of adults, regardless of nicotine pre-exposure. During withdrawal, ACh levels in the NAcc were increased in a similar manner in adolescent and naïve adult rats. However, this increase in ACh was absent in pre-exposed adult rats. These neurochemical differences do not appear to be related to nicotine metabolism, as plasma cotinine levels were similar across all experimental groups. The second study revealed that AChE activity in the NAcc was highest in adolescents versus both groups of adult rats, regardless of their previous exposure to nicotine. In conclusion, our results suggest that nicotine exposure during adolescence enhances baseline ACh in the NAcc. However, the finding that ACh levels were similar during withdrawal in adolescent and adult rats suggests that the enhanced vulnerability to tobacco use during adolescence is not likely related to age differences in withdrawal-induced increases in cholinergic transmission. Our results also suggest that exposure to nicotine during adolescence suppresses withdrawal-induced increases in cholinergic responses during withdrawal. Taken together, this report illustrates important short- and long-term changes within cholinergic systems that may contribute to the enhanced susceptibility to tobacco use during adolescence.
Publication DateAugust 1, 2014
Citation InformationLaura O'Dell. "Cholinergic transmission during nicotine withdrawal is influenced by age and pre-exposure to nicotine: Implications for teenage smoking" Developmental Neuroscience Vol. 36 (2014)
Available at: http://works.bepress.com/laura_odell/55/