Developmental Neurotoxicity of Nicotine

Levin, Edward D.; Slotkin, Theodore A.

doi:10.1016/b978-012648860-9.50043-1

Cited by 57 publications

(89 citation statements)

References 204 publications

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“…Indeed, with fetal exposure, nicotine elicits specific, receptormediated effects on cell replication, differentiation, and synaptogenesis that contribute to its neurobehavioral teratogenicity (Levin and Slotkin, 1998;Slotkin, 1992Slotkin, , 1998Slotkin, , 1999, and at least some of these mechanisms persist into adolescence (Slotkin, 2002). Although direct evidence for adolescent brain cell injury caused by low-dose nicotine exposure is being pursued in a separate study (AbreuVillaça et al, 2003), the current results for ChAT provide some evidence of neurotoxicant actions.…”

Section: Is Nicotine a Neurotoxin In The Adolescent Brain?mentioning

confidence: 76%

“…Even more intriguing, the promotional effect on ChAT in the latter two regions was not a monotonic function of dose, but rather displayed hormesis, with reversal of the effect at higher doses, a typical finding for other aspects of nicotine's biological effects (Furst, 1987). In fact, the biphasic effects on ChAT might be expected from the fact that the activation of nAChRs serves a trophic role in neurodevelopment (Coronas et al, 2000;Hohmann and Berger-Sweeney, 1998;Hohmann et al, 1988;Navarro et al, 1989;Pugh and Margiotta, 2000), while at the same time, excessive stimulation disrupts patterns of cell replication, differentiation, and synaptogenesis (Levin and Slotkin, 1998;Slotkin, 1992Slotkin, , 1998Slotkin, , 1999, progressing at high levels to outright cell damage (Abrous et al, 2002;Slotkin, 1992Slotkin, , 1998Trauth et al, 2000b). The fact that neuronal cell replication continues into adolescence in late-developing regions may render these particular areas especially vulnerable to hormetic effects of nicotine (Altman and Bayer, 1990;McWilliams and Lynch, 1983;Zahalka et al, 1992Zahalka et al, , 1993.…”

Section: Is Nicotine a Neurotoxin In The Adolescent Brain?mentioning

confidence: 99%

“…In spite of these facts, only recently has basic research focused on the biological substrates that may underlie the susceptibility of the adolescent brain to nicotine dependence (Slotkin, 2002). It is well established that nicotine exposure during prenatal development induces cognitive and behavioral deficits that reflect deleterious actions of nicotine that alter cell proliferation and differentiation, synaptic maturation, and cell signaling (Levin and Slotkin, 1998;Slotkin, 1992Slotkin, , 1998Slotkin, , 1999. Brain development continues into adolescence, specifically encompassing neuroproliferation, apoptosis, and synaptic rearrangement (Bayer, 1983;Bayer et al, 1982;Huttenlocher, 1990).…”

Section: Introductionmentioning

confidence: 99%

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Short-Term Adolescent Nicotine Exposure has Immediate and Persistent Effects on Cholinergic Systems: Critical Periods, Patterns of Exposure, Dose Thresholds

Abreu‐Villaça

Seidler

Qiao

et al. 2003

Neuropsychopharmacol

138

101

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In adolescents, the symptoms of nicotine dependence can appear well before the onset of habitual smoking. We investigated short-term nicotine exposure in adolescent rats for corresponding cholinergic alterations. Beginning on postnatal day 30, rats were given a 1-week regimen of nicotine infusions or twice-daily injections, at doses (0.6, 2, and 6 mg/kg/day) set to achieve plasma levels found in occasional to regular smokers. In the cerebral cortex, midbrain, and hippocampus, we assessed nicotinic cholinergic receptor (nAChR) binding, choline acetyltransferase (ChAT) activity, a constitutive marker for cholinergic nerve terminals, and [ 3 H]hemicholinium-3 (HC-3) binding to the high-affinity choline transporter, which responds to cholinergic synaptic stimulation. nAChR upregulation was observed with either administration route, even at the lowest dose; in the hippocampus, increases could be detected with as little as 2 days' treatment at 0.6 mg/kg/day. In the midbrain, upregulation was still significant even 1 month post-treatment. Adolescent nicotine treatment also produced lasting decrements in HC-3 binding that were separable from effects on ChAT, suggesting cholinergic synaptic impairment. Again, these effects were obtained at the lowest dose and remained significant 1 month post-treatment. Our results indicate that in adolescence, even a brief period of continuous or intermittent nicotine exposure, elicits lasting alterations in cholinergic systems in brain regions associated with nicotine dependence. As the effects are detected at exposures that produce plasma concentrations as little as one-tenth of those in regular smokers, the exquisite sensitivity of the adolescent brain to nicotine may contribute to the onset of nicotine dependence even in occasional smokers.

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Section: Is Nicotine a Neurotoxin In The Adolescent Brain?mentioning

confidence: 76%

Section: Is Nicotine a Neurotoxin In The Adolescent Brain?mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Short-Term Adolescent Nicotine Exposure has Immediate and Persistent Effects on Cholinergic Systems: Critical Periods, Patterns of Exposure, Dose Thresholds

Abreu‐Villaça

Seidler

Qiao

et al. 2003

Neuropsychopharmacol

138

101

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“…The absence of these receptors from the zygote stage onward can cause a variety of cascading effects. Nicotinic receptors play important roles in the control of neurodevelopment (Levin and Slotkin, 1998;Broide and Leslie, 1999). Eliminating select populations of nicotinic receptors can have effects on neurodevelopment that last a lifetime.…”

Section: Pharmacological and Genetic Approaches To Receptor Subtype Amentioning

confidence: 99%

Nicotinic receptor subtypes and cognitive function

2002

Self Cite

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ABSTRACT:Nicotinic receptor systems are involved in a wide variety of behavioral functions including cognitive function. Nicotinic medications may provide beneficial treatment for cognitive dysfunction such as Alzheimer's disease, schizophrenia, and attention deficit hyperactivity disorder (ADHD). Nicotine has been shown to improve attentional performance in all of these disorders. Better efficacy with fewer side effects might be achieved with novel nicotinic ligands selective for particular nicotinic subtypes. To develop these novel selective nicotinic ligands it is important to use animal models to determine the critical neurobehavioral bases for nicotinic involvement in cognitive function. Nicotineinduced cognitive improvement in rats is most consistently seen in working memory tasks. We have found that both acute and chronic nicotine administration significantly improves working memory performance of rats in the radial-arm maze. The pharmacologic and anatomic mechanisms for this effect have been examined in our laboratory in a series of local drug infusion studies. Both ␣4␤2 and ␣7 nicotinic receptors in the ventral hippocampus and basolateral amygdala are involved in working memory function. Working memory impairments were caused by local infusion of either ␣4␤2 or ␣7 antagonists. Ventral hippocampal ␣4␤2 blockade-induced working memory deficits are reversed by chronic systemic nicotine treatment, while ventral hippocampal ␣7 blockade-induced working memory deficits were not found to be reversed by the same nicotine regimen. Interestingly, ␣4␤2 and ␣7 induced deficits were not found to be additive in either the ventral hippocampus or the basolateral amygdala. In fact, in the amygdala, ␣7 antagonist cotreatment actually reversed the working memory impairment caused by ␣4␤2 antagonist administration. These studies of the neural nicotinic mechanisms underlying cognitive function are key for opening avenues for development of safe and effective nicotinic treatments for cognitive dysfunction.

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“…Prenatal nicotine exposure via maternal smoking during pregnancy (MSDP) has been described as "the most widespread prenatal drug insult in the world" (Levin & Slotkin, 1998). Despite pervasive medical and societal sanctions against smoking during pregnancy (Logan & Spencer, 1996), it is estimated that between 11% and 30% of women continue to smoke during pregnancy in the United States (Martin, Hamilton, Ventura, Menacker, & Park, 2002).…”

Section: Introductionmentioning

confidence: 99%

Maternal Smoking During Pregnancy and Offspring Brain Structure and Function: Review and Agenda for Future Research

Bublitz

Stroud

2011

Nicotine & Tobacco Research

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Introduction: Maternal smoking during pregnancy (MSDP) has been associated with long-term neurobehavioral and cognitive deficits in offspring. Animal models demonstrate alterations in brain structure and function following prenatal nicotine exposure. However, few studies have assessed the relationship between MSDP and brain development in humans. Therefore, the aims of this review are (a) to synthesize findings from the small number of human studies investigating effects of MSDP on offspring brain development and (b) to outline an agenda for future research in this nascent area. Methods:We searched MEDLINE and Psychinfo databases for human studies of MSDP and offspring brain structure and/or function.Results: Eleven studies meeting our search criteria were identified; 6 studies investigated effects of MSDP on brain structure; 5 examined effects on brain function. Across studies, MSDP was associated with decreased volume/thickness of the cerebellum and corpus callosum, increased auditory brainstem responses, and lack of coordination across brain regions during information and auditory processing. Conclusions:Results from the small number of human studies revealed effects of MSDP on brain structure and function, highlighting potential neural pathways linking MSDP and offspring neurobehavioral and cognitive deficits. Given the limited amount of research in this area, we propose an agenda for future research. Gold standard studies would utilize longitudinal designs, integrated biological and maternal report measures of MSDP, and repeated measures of brain structure/function and neurobehavioral deficits across key developmental periods.

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Developmental Neurotoxicity of Nicotine

Cited by 57 publications

References 204 publications

Short-Term Adolescent Nicotine Exposure has Immediate and Persistent Effects on Cholinergic Systems: Critical Periods, Patterns of Exposure, Dose Thresholds

Short-Term Adolescent Nicotine Exposure has Immediate and Persistent Effects on Cholinergic Systems: Critical Periods, Patterns of Exposure, Dose Thresholds

Nicotinic receptor subtypes and cognitive function

Maternal Smoking During Pregnancy and Offspring Brain Structure and Function: Review and Agenda for Future Research

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