Neurochemical alterations produced by daily nicotine exposure in periadolescent vs. adult male rats

Collins, Stephanie L.; Wade, Dean; Ledon, Jennifer; Izenwasser, Sari

doi:10.1016/j.ejphar.2004.08.039

Cited by 54 publications

(41 citation statements)

References 59 publications

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“…Sex differences in up-regulation of nicotinic receptors have already been shown for experimenter-imposed adolescent nicotine administration [39]. However, other research has found that nicotine administration during adolescence does not cause the increase in nicotinic receptors as much it does in adults [8]. One critical difference in this study from the earlier one [39] is that one week of daily nicotine injections was given in the Collins study while four weeks of chronic osmotic minipump infusions was given in the Trauth study.…”

Section: Discussioncontrasting

confidence: 45%

Adolescent vs. adult-onset nicotine self-administration in male rats: Duration of effect and differential nicotinic receptor correlates

Levin

Lawrence

Petro

et al. 2007

Neurotoxicology and Teratology

131

105

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Adolescence is the life stage when tobacco addiction typically begins. Adolescent neurobehavioral development may be altered by nicotine self-administration in a way that persistently potentiates addiction. Previously, we showed that female adolescent rats self-administer more nicotine than do adults and that the increased nicotine intake then persists through the transition to adulthood [23]. In the current study, male Sprague-Dawley rats were given access to nicotine via the standard operant IV self-administration procedure (nicotine bitartrate dose of 0.03 mg/kg/infusion). One group of male rats started during adolescence the other group started in young adulthood. After the end of the fourweek period of self-administration brain regions of the rats were assessed for α4β2 nicotinic receptor binding. We found that male rats, like females, show higher nicotine self-administration when starting during adolescence as compared to starting in adulthood (p<0.001). Indeed, the effect in adolescent males was even greater than that in females, with more than triple the rate of nicotine selfadministration vs. the adult-onset group during the first two weeks. The adolescent onset nicotineself-administering rats also had significantly greater high affinity nicotinic receptor binding in the midbrain and the striatum, whereas hippocampal binding did not differ between the age groups. Striatal values significantly correlated with nicotine self-administration during the first two weeks in the adult-onset group but not the adolescent-onset rats, suggesting that the differences in selfadministration may depend in part on underlying disparities in synaptic responses to nicotine. After the initial two weeks, nicotine self-administration in male rats declined toward adult-like levels, as the adolescent rats approached adulthood. This study showed that adolescent male rats selfadminister significantly more nicotine than do male adult rats, but that adolescent-onset nicotine selfadministration in male rats declines over weeks of continued use to approach adult-onset levels. In a previous study, we found that female rats also show greater nicotine self-administration with adolescent onset vs. adult onset, but that the females continued higher rates of self-administration into adulthood. Our results thus reinforce the concept that the adolescent brain is unusually receptive to the effects of nicotine in a manner that reinforces the potential for addiction.

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Section: Discussioncontrasting

confidence: 45%

Adolescent vs. adult-onset nicotine self-administration in male rats: Duration of effect and differential nicotinic receptor correlates

Levin

Lawrence

Petro

et al. 2007

Neurotoxicology and Teratology

131

105

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“…Nicotine treatment during periadolescence in mice has been shown to result in downregulation of GluR2/3 subunits in the striatum, whereas nicotine treatment in adulthood had the opposite effect [2]. Chronic nicotine administration also causes increased dopamine transporter density and decreased in serotonin transporter binding in the striatum of periadolescent, but not adult, rats [20]. Taken together, these studies suggest that adolescent exposure to nicotine causes unique changes in brain reward circuitry.…”

Section: Introductionsupporting

confidence: 50%

“…Adolescent treatment with nicotine during a sensitive period of striatal maturation may produce long-term changes in this circuitry. Support for this concept has been provided by recent studies showing long-term changes in striatal dopamine transporters and AMPA receptors following chronic adolescent nicotine exposure [2,20]. Further neurochemical studies will be required to show whether our brief intravenous nicotine exposure paradigm produces similar changes in striatum.…”

Section: Neural Mechanismsmentioning

confidence: 74%

Low dose nicotine treatment during early adolescence increases subsequent cocaine reward

McQuown

Belluzzi

Leslie

2007

Neurotoxicology and Teratology

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Adolescence is a critical period for the initiation of drug use, starting with tobacco and alcohol and progressing to marijuana and other illicit drugs. These findings have led to the suggestion that tobacco and alcohol are 'gateway' drugs that sensitize maturing reward pathways to the effects of illicit substances such as cocaine. To test this hypothesis, we have examined whether low-dose nicotine pretreatment alters acquisition of cocaine self-administration in adolescents more than in adults. Male and female Sprague-Dawley rats, aged postnatal day (P) 28 or P86, were given two daily intravenous injections of nicotine (0.03 mg/kg/0.1 ml) or saline for four days. At P32 and P90, rats were placed in self-administration chambers and tested for acquisition of cocaine (0.2 or 0.5 mg/kg/inj) for five days. Data were collapsed across cocaine dose and sex since there was no significant effect of these variables. Adolescent rats pretreated with nicotine exhibited significantly greater cocaine-reinforced responding as compared to saline controls or adults (p < 0.01). This drug pretreatment effect did not generalize to all rewards, since nicotine did not increase responding for sucrose pellets in adolescents. These findings provide evidence that the adolescent brain is uniquely vulnerable to the effects of nicotine on subsequent drug reward.

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“…Importantly, many of these features emerge in adolescence (Navarro et al, 1989;Slotkin, 1992Slotkin, , 1998Slotkin, , 1999Slotkin, , 2004Zahalka et al, 1992), when access to tobacco products becomes available. At that stage, nicotine intake partially relieves the deficiencies; although the adolescent brain is highly responsive to nicotine (Abreu-Villaça et al, 2003a-c; Collins et al, 2004;Elliott et al, 2005;Faraday et al, 2001;Slotkin, 2002), prenatal nicotine exposure produces lasting desensitization (Abreu-Villaça et al, 2004b;Seidler et al, 1992), so that the offspring of smokers will tend toward much higher consumption to obtain the desired effect, which in turn extends and expands the degree of damage and reprogramming of neural circuits (Abreu-Villaça et al, 2004a), augmenting and cementing the permanent changes in synaptic function and behavioral performance. When these individuals attempt to quit, they are consequently thrown into a worsened degree of cognitive impairment, depression, and loss of reward than if they had never smoked at all, as revealed in recent findings (Jacobsen et al, 2006).…”

Section: Resultsmentioning

confidence: 99%

“…Brain development continues into adolescence and recent work indicates that many of the mechanisms by which nicotine adversely affects the fetus still operate in the adolescent brain, producing similar (albeit lesser) functional anomalies and even outright neurotoxicity (Slotkin, 2002). In addition, the adolescent brain is much more responsive to nicotine than is the adult, enhancing the synaptic and behavioral responses that contribute to dependence and addiction (Abreu-Villaça et al, 2003a-c;Collins et al, 2004;Elliott et al, 2005;Faraday et al, 2001;Slotkin, 2002), echoing observations made in adolescent smokers (DiFranza et al, 2000(DiFranza et al, , 2002a. Furthermore, the synaptic alterations evoked by fetal nicotine exposure affect the response to nicotine in adolescence (Abreu-Villaça et al, 2004a, b;Jacobsen et al, 2006;Slotkin et al, 2006), likely contributing to the subpopulation in the offspring of smokers that are especially vulnerable to nicotine dependence (Jacobsen et al, 2006;Kandel et al, 1994;Niaura et al, 2001;Porath and Fried, 2005;Roberts et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Permanent, Sex-Selective Effects of Prenatal or Adolescent Nicotine Exposure, Separately or Sequentially, in Rat Brain Regions: Indices of Cholinergic and Serotonergic Synaptic Function, Cell Signaling, and Neural Cell Number and Size at 6 Months of Age

Slotkin

MacKillop

Rudder

et al. 2006

Neuropsychopharmacol

146

113

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Nicotine is a neuroteratogen that disrupts neurodevelopment and synaptic function, with vulnerability extending into adolescence. We assessed the permanence of effects in rats on indices of neural cell number and size, and on acetylcholine and serotonin (5HT) systems, conducting assessments at 6 months of age, after prenatal nicotine exposure, adolescent exposure, or sequential exposure in both periods. For prenatal nicotine, indices of cell number and size showed few abnormalities by 6 months, but there were persistent deficits in cerebrocortical choline acetyltransferase activity and hemicholinium-3 binding to the presynaptic choline transporter, a pattern consistent with cholinergic hypoactivity; these effects were more prominent in males than females. The expression of 5HT receptors also showed permanent effects in males, with suppression of the 5HT 1A subtype and upregulation of 5HT 2 receptors. In addition, cell signaling through adenylyl cyclase showed heterologous uncoupling of neurotransmitter responses. Nicotine exposure in adolescence produced lasting effects that were similar to those of prenatal nicotine. However, when animals were exposed to prenatal nicotine and received nicotine subsequently in adolescence, the adverse effects then extended to females, whereas the net effect in males was similar to that of prenatal nicotine by itself. Our results indicate that prenatal or adolescent nicotine exposure evoke permanent changes in synaptic function that transcend the recovery of less-sensitive indices of structural damage; further, prenatal exposure sensitizes females to the subsequent adverse effects of adolescent nicotine, thus creating a population that may be especially vulnerable to the lasting behavioral consequences of nicotine intake in adolescence.

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Neurochemical alterations produced by daily nicotine exposure in periadolescent vs. adult male rats

Cited by 54 publications

References 59 publications

Adolescent vs. adult-onset nicotine self-administration in male rats: Duration of effect and differential nicotinic receptor correlates

Adolescent vs. adult-onset nicotine self-administration in male rats: Duration of effect and differential nicotinic receptor correlates

Low dose nicotine treatment during early adolescence increases subsequent cocaine reward

Permanent, Sex-Selective Effects of Prenatal or Adolescent Nicotine Exposure, Separately or Sequentially, in Rat Brain Regions: Indices of Cholinergic and Serotonergic Synaptic Function, Cell Signaling, and Neural Cell Number and Size at 6 Months of Age

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