Diminished nicotine withdrawal in adolescent rats: implications for vulnerability to addiction

O’Dell, Laura E.; Bruijnzeel, Adrie W.; Smith, Ron T.; Parsons, Loren H.; Merves, Michele L.; Goldberger, Bruce A.; Richardson, H. G.; Koob, George F.; Markou, Athina

doi:10.1007/s00213-006-0383-6

Cited by 138 publications

(151 citation statements)

References 42 publications

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“…The present findings are consistent with our previous work demonstrating that adolescent rats display less physical signs of nicotine withdrawal relative to adults [15,16]. Specifically, adolescent rats display fewer overt physical signs of precipitated withdrawal than adults across a range mecamylamine doses to produce withdrawal and a range of nicotine doses to produce dependence.…”

Section: Discussionsupporting

confidence: 92%

“…Adolescent rats gain weight at a faster rate than adults, such that one might expect that adolescents might have lower daily levels of nicotine relative to adults. However, our previous work determining equivalent blood plasma levels of nicotine was conducted 7 days after the rats were prepared with minipumps and this is when the rats began conditioning in the present study [16]. Thus, we expect that these age groups had equivalent blood levels of nicotine when the conditioning phase of the experiment began.…”

Section: Methodsmentioning

confidence: 81%

“…The rationale for using a higher dose of nicotine in adolescents is based on work from our laboratory [16] and others [25] demonstrating that a 1.5 fold higher concentration of nicotine is needed to produce equivalent blood plasma levels in adolescent and adult rats with nicotine minipumps. Our previous work demonstrated that a nicotine dose of 4.7 mg/kg/day in adolescents results in 76.2±7 ng/ml of plasma nicotine and a nicotine dose of 3.2 mg/kg/day in adults results in 65.4±9 ng/ml of plasma nicotine 7 days after the rats were prepared with minipumps [16]. Adolescent rats gain weight at a faster rate than adults, such that one might expect that adolescents might have lower daily levels of nicotine relative to adults.…”

Section: Methodsmentioning

confidence: 99%

“…Studies using animal models indicate that enhanced reinforcing effects of nicotine may contribute to tobacco use during adolescence [2,8,13,25]. Recent work demonstrates that the physical signs of nicotine withdrawal are lower in adolescent relative to adult rats [15,16]. These findings suggest that there are likely different mechanisms that drive smoking behavior in adolescent and adult smokers.…”

Section: Introductionmentioning

confidence: 99%

“…This is based on our finding that adolescent rats do not display elevated intracranial self-stimulation (ICSS) reward thresholds following mecamylamine administration relative to saline controls [16]. ICSS involves allowing a rat to self-administer small amounts of electrical current into reward-related structures.…”

Section: Introductionmentioning

confidence: 99%

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Adolescent nicotine exposure produces less affective measures of withdrawal relative to adult nicotine exposure in male rats

O’Dell

Torres

Natividad

et al. 2007

Neurotoxicology and Teratology

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Vulnerability to nicotine addiction is significantly increased in individuals who begin smoking during adolescence; however, the underlying mechanisms of this phenomenon remain unclear. This study examined the motivational effects of nicotine withdrawal in adolescent and adult (PND 60-75) rats using the conditioned place aversion paradigm. Male Wistar rats were tested for their initial preference for either of two distinct compartments of our conditioning apparatus. Rats were then implanted with subcutaneous (sc) pumps that produce equivalent blood plasma levels of nicotine for 14 days. Conditioning was conducted over the last 8 days of nicotine exposure. Rats received the nicotinic antagonist mecamylamine (1.5 or 3.0 mg/kg, sc) to precipitate withdrawal in their initially preferred compartment, and on alternate days they received saline in their non-preferred compartment. Following conditioning, rats were re-tested for their preference for each compartment. A subsequent study was conducted to examine potential developmental differences in learning place aversion produced by another aversive stimulus, lithium chloride (LiCl). Rats received LiCl (0, 10, 30, or 100 mg/kg, sc) in their initially preferred side using similar conditioning procedures. Adults displayed robust place aversion produced by nicotine withdrawal. This effect was lower in adolescent rats even in a group of young rats that received 7 additional days of nicotine exposure prior to conditioning. This developmental difference was specific to nicotine withdrawal since there were no differences between adolescents and adults in learning place aversion with LiCl. Our findings demonstrating reduced effects of nicotine withdrawal constitute a powerful basis for the increased vulnerability to nicotine dependence during adolescence.

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Section: Discussionsupporting

confidence: 92%

Section: Methodsmentioning

confidence: 81%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Adolescent nicotine exposure produces less affective measures of withdrawal relative to adult nicotine exposure in male rats

O’Dell

Torres

Natividad

et al. 2007

Neurotoxicology and Teratology

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Differential sensitivity to the effects of nicotine and bupropion in adolescent and adult male OF1 mice during social interaction tests

Gómez

Carrasco

Redolat

2008

Aggressive Behavior

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Few studies have compared the action of both nicotine (NIC) and bupropion (BUP), an antidepressant used to treat NIC dependence, on social and aggressive behavior at different ages. This study aims to determine whether these drugs produce differential effects in adolescent (postnatal day: 36-37) and adult (postnatal day: 65-66) mice that have been housed individually for 2 weeks in order to induce aggressive behavior. Mice received BUP (40, 20, or 10 mg/kg), NIC (1, 0.5, and 0.25 mg/kg as base), or vehicle earlier to a social interaction test. BUP (40 mg/kg) decreased social investigation and increased nonsocial exploration in both adolescent and adult mice. The same effects were also observed in adult mice administered with a lower dose of the same drug (20 mg/kg). In adolescents, NIC (1 mg/kg) decreased social investigation, but this effect did not reach statistical significance in adults. In conclusion, a differential sensitivity to the effects of NIC or BUP emerged in some of the behavioral categories when the two age groups were compared.

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Nicotine Vapor Method to Induce Nicotine Dependence in Rodents

Kallupi

George

2017

CP Neuroscience

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Nicotine, the main addictive component of tobacco, induces potentiation of brain stimulation reward, increases locomotor activity and induces conditioned place preference. Nicotine cessation produces a withdrawal syndrome that can be relieved by nicotine replacement therapy. In the last decade, the market for electronic cigarettes has flourished, especially among adolescents. The nicotine vaporizer or electronic nicotine delivery system is a battery-operated device that simulates the experience of tobacco smoking without inhaling smoke. The device is designed to be an alternative for conventional cigarettes that emits vaporized nicotine that is inhaled by the user. This report describes a procedure to vaporize nicotine in the air to produce blood nicotine levels in rodents that are clinically relevant to those that are observed in humans and produce dependence. We also describe how to construct the apparatus to deliver nicotine vapor in a stable, reliable, and consistent manner and how to analyze air for nicotine content.

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Diminished nicotine withdrawal in adolescent rats: implications for vulnerability to addiction

Abstract: The negative effects of nicotine withdrawal are lower during adolescence relative to later periods of development. Both the enhanced rewarding effects and the diminished nicotine withdrawal likely contribute to the rapid development of nicotine use during adolescence.

Cited by 138 publications

References 42 publications

Adolescent nicotine exposure produces less affective measures of withdrawal relative to adult nicotine exposure in male rats

Adolescent nicotine exposure produces less affective measures of withdrawal relative to adult nicotine exposure in male rats

Differential sensitivity to the effects of nicotine and bupropion in adolescent and adult male OF1 mice during social interaction tests

Nicotine Vapor Method to Induce Nicotine Dependence in Rodents

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