Adolescent Rats Self-Administer Less Nicotine Than Adults at Low Doses

Abstract

Introduction: Although nearly 90% of current smokers initiated tobacco use during adolescence, little is known about reinforcement by nicotine in adolescents. Researchers are currently investigating whether a potential public health policy setting a tobacco product standard with very low nicotine levels would improve public health, and it is essential to understand whether data generated in adults translates to adolescents, particularly as it relates to the threshold dose of nicotine required to support smoking. The present study compared self-administration of low doses of nicotine between adolescent and adult rats. Methods: Adolescent (postnatal day [P] 30) and adult (P90) male and female rats were allowed to nosepoke to receive intravenous infusions of nicotine (3-100 μg/kg/infusion) during 16 daily 1-hour sessions. Results: At 10 μg/kg/infusion nicotine, adolescent rats earned significantly fewer infusions than adults. When responding for 30 μg/kg/infusion nicotine, rats of both ages earned a similar number of infusions; however, there were subtle differences in the distribution of infusions across the 1-hour session. No sex differences were apparent in either age group at any dose. Conclusions: These results demonstrate that adolescent rats are less sensitive than adults to the primary reinforcing effects of nicotine. However, at nicotine doses that support self-administration in both age groups, adolescent and adult rats do not differ in acquisition or number of infusions earned. These results suggest that reducing nicotine levels in cigarettes to a level that does not support smoking in adults may be sufficient to reduce the acquisition of smoking in adolescents. Implications: The results of the present studies demonstrate that adolescent rats are less sensitive than adults to the primary reinforcing effects of nicotine. These results suggest that reducing nicotine levels in cigarettes to a level that does not support smoking in adults will be sufficient to reduce the acquisition of smoking in adolescents.

Self-administration of nicotine and cigarette smoke extract in adolescent and adult rats

“…Therefore, we believe that the lack of age effects at FR5 are due to the FR schedule being more difficult and that the differences observed at FR1 were not robust and should be interpreted with care. Our findings are consistent with other studies that have shown age differences in responding for low doses of nicotine at differing schedules of reinforcement (Schassburger et al, 2016; Shram et al, 2008). However, in contrast to these other studies, we have found adolescent rats to be more sensitive to the reinforcing effect of low doses of drug at the FR1 schedule.…”

Self-administration of Smokeless Tobacco Products in Rats

“…19,20,50 However, this finding contrasts with other studies showing lower rates of acquisition and nicotine intake under FR schedules and lower breaking points under a PR schedule in adolescents compared to adults. 51-53 This discrepancy may be due to the use of a higher training dose of nicotine and different strain of rat in the present study, as age differences in nicotine self-administration can depend on these factors. 52,53 It is also important to note that adolescent rats were young adults by the end of the PR phase in Experiment 1.…”

Reward-centricity and attenuated aversions: An adolescent phenotype emerging from studies in laboratory animals

“…Likewise, numerous laboratories have observed that under a variety of circumstances adolescent rats exhibit greater intravenous (i.v.) self-administration than adults for cocaine (Anker and Carroll, 2010; Wong et al, 2013), amphetamine (Shahbazi et al, 2008), methamphetamine (Anker et al, 2012), and nicotine (Ahsan et al, 2014; Levin et al, 2011; Natividad et al, 2013), although it should be mentioned that some negative findings have emerged (e.g., for cocaine: Harvey et al, 2009; for nicotine: Schassburger et al, 2016; Shram et al, 2008a; 2008b). Critical variables influencing age differences in drug self-administration may include age of initiation during adolescence (with early adolescence perhaps being a particularly sensitive period – Levin et al, 2011), length of access period (Anker et al, 2012), dose and operant schedule (Shram et al, 2008a; and 2008b), dependent measure of focus (e.g., self-administration per se versus drug-seeking behavior – Doherty and Frantz, 2012), and whether animals were group- or isolate-housed (the latter has been reported to increase drug/alcohol abuse vulnerability in adolescent rodents – Butler et al, 2016).…”