Adolescent-onset nicotine self-administration modeled in female rats

Levin, Edward D.; Rezvani, Amir H.; Montoya, Daniel; Rose, Jed E.; Swartzwelder, H. Scott

doi:10.1007/s00213-003-1486-y

Cited by 197 publications

(190 citation statements)

References 44 publications

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“…These present findings with the FR1 and FR2 reinforcement schedules are consistent with the study by Belluzzi et al (2005) in which no age differences for nicotine selfadministration were observed under the FR1 reinforcement schedule. Our results are also partly consistent with the study by Levin et al (2003), in which adolescent and adult female rats earned a similar number of nicotine infusions during the early phase of training, when the younger rats were in late adolescence (P43-46).…”

Section: Nicotine Self-administration In Adolescent and Adult Ratssupporting

confidence: 92%

“…Using conditioned place preference (CPP) and conditioned taste avoidance (CTA) procedures, we and others reported that adolescent rats are more sensitive to the rewarding effects of nicotine and less sensitive to its aversive effects than adult rats (Vastola et al, 2002;Belluzzi et al, 2004;Torrella et al, 2004;Wilmouth and Spear, 2004;Shram et al, 2006). Furthermore, several investigators reported that adolescent rats may acquire nicotine self-administration faster than adult rats (Levin et al, 2003;Belluzzi et al, 2005;Chen et al, 2007). However, the degree to which the findings from these self-administration studies reflect increased vulnerability to nicotine's rewarding effects in adolescents is unknown.…”

Section: Introductionmentioning

confidence: 99%

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Nicotine Self-Administration, Extinction Responding and Reinstatement in Adolescent and Adult Male Rats: Evidence Against a Biological Vulnerability to Nicotine Addiction during Adolescence

Shram

Funk

et al. 2007

Neuropsychopharmacol

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Initiation of smoking behavior typically occurs during adolescence and rarely occurs during adulthood. Despite this epidemiological evidence, relatively little is known about possible neurobiological differences in the response to nicotine in adolescents that might make them more vulnerable to nicotine addiction. In the current study, we assessed nicotine self-administration under fixed ratio (FR) and progressive ratio (PR) reinforcement schedules in adolescent (postnatal day (P) 33-35) and adult (P91-94) rats. We then assessed extinction and reinstatement of nicotine seeking in adulthood in rats that initiated nicotine self-administration during either adolescence or adulthood. Nicotine self-administration (0.03 mg/kg/infusion, i.v.) was higher in adult rats than in adolescent rats under FR5 and PR reinforcement schedules; no age differences in nicotine self-administration were observed under FR1 or FR2 reinforcement schedules. In contrast, saccharin self-administration under FR5 and PR reinforcement schedules was similar in both age groups, potentially ruling out age differences in general performance. Rats that initiated nicotine self-administration as adults demonstrated a greater resistance to extinction of nicotine taking behavior when saline was substituted for nicotine than rats that initiated self-administration as adolescents. Reinstatement of nicotine seeking following nicotine priming injections (0.075, 0.15, 0.3 mg/kg, s.c.) was independent of the age of onset of nicotine self-administration. The present data from established rat models of drug self-administration and drug relapse suggest that nicotine is less reinforcing in adolescent compared with adult rats and that processes other than the reinforcing effects of nicotine may be involved in the greater susceptibility to smoking during the adolescent developmental stage.

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Section: Nicotine Self-administration In Adolescent and Adult Ratssupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Nicotine Self-Administration, Extinction Responding and Reinstatement in Adolescent and Adult Male Rats: Evidence Against a Biological Vulnerability to Nicotine Addiction during Adolescence

Shram

Funk

et al. 2007

Neuropsychopharmacol

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“…Without experiencing any negative effects of nicotine to deter smoking behavior, adolescents are more likely to continue smoking. Furthermore, there is a large body of literature demonstrating that adolescent rats are more sensitive to the reinforcing [2,13] and stimulant [8] effects of nicotine. Taken together, it appears that adolescent rats are more sensitive to the positive effects of nicotine reward and less sensitive to the negative effects of nicotine withdrawal.…”

Section: Discussionmentioning

confidence: 99%

“…In general, it seems that smoking behavior is motivated by both the positive reinforcing effects of nicotine and avoidance of the negative effects associated with nicotine withdrawal. 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].…”

Section: Introductionmentioning

confidence: 99%

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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“…Adolescence appears to be a critical period for the initiation of smoking in humans (Eissenberg and Balster, 2000), and the acute effects of nicotine enhance rat locomotor activity in early adolescent rats and suppress it at later ages (Vastola et al, 2002;Faraday et al, 2003;Belluzzi et al, 2004). Early adolescence also appears to be a period of increased sensitivity to the rewarding effects of nicotine (Adriani et al, 2002;Vastola et al, 2002;Belluzzi et al, 2004), and Levin and co-workers have shown that female rats, aged P54, have higher rates of nicotine intake than do older animals (Levin et al, 2003). Thus, we have evaluated the possible synergistic interactions of acetaldehyde and nicotine in a rat self-administration acquisition test in both juvenile and adult rats.…”

Section: Introductionmentioning

confidence: 99%

Acetaldehyde Enhances Acquisition of Nicotine Self-Administration in Adolescent Rats

Belluzzi

Wang

Leslie

2004

Neuropsychopharmacol

220

213

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Tobacco use has one of the highest rates of addiction and relapse of any abused drug. Paradoxically, however, in animal models of reinforcement nicotine appears weak compared to other abused drugs. We report here that acetaldehyde, a major component of tobacco smoke, enhances nicotine self-administration. Juvenile and adult male rats were implanted with intravenous catheters and tested for self-administration 4 days later at postnatal day 27 or 90, respectively. Animals were tested, without prior response training, in five daily 3-h sessions where each nose-poke delivered an intravenous injection followed by a 60-s timeout. Animals (11-13/group) were offered one of the following solutions: nicotine (30 mg/kg/injection), acetaldehyde (16 mg/kg/inj), nicotine (30 mg/kg/inj) þ acetaldehyde (16 mg/kg/inj), or saline. The youngest animals responded significantly more for nic þ acet than for saline or for either drug alone. Responding at the reinforced hole was significantly higher than at the nonreinforced hole or at the reinforced hole during noncontingent injections of nic þ acet. Tests with receptor antagonists indicated that these drug effects are mediated by central, but not peripheral, nicotinic receptors. There was an age-related decline in self-administration of nic þ acet, but not for cocaine. Taken together, these results indicate that acetaldehyde, at the low concentrations found in tobacco smoke, interacts with nicotine to increase responding in a stringent self-administration acquisition test where nicotine alone is only weakly reinforcing, and that adolescent animals are more sensitive to these actions than adults. Animal models of tobacco addiction could be improved by combining acetaldehyde, and possibly other smoke components, with nicotine to more accurately reflect the pharmacological profile of tobacco smoke.

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Adolescent-onset nicotine self-administration modeled in female rats

Cited by 197 publications

References 44 publications

Nicotine Self-Administration, Extinction Responding and Reinstatement in Adolescent and Adult Male Rats: Evidence Against a Biological Vulnerability to Nicotine Addiction during Adolescence

Nicotine Self-Administration, Extinction Responding and Reinstatement in Adolescent and Adult Male Rats: Evidence Against a Biological Vulnerability to Nicotine Addiction during Adolescence

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

Acetaldehyde Enhances Acquisition of Nicotine Self-Administration in Adolescent Rats

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