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

Abstract

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.

A Role For The Prefrontal Cortex In Heroin-Seeking After Forced Abstinence By Adult Male Rats But Not Adolescents

“…This result was independently replicated with cocaine-seeking (Anker and Carroll, 2010). It suggests that adolescent rats are less sensitive to some enduring drug effects, an interpretation supported by age differences in several cocaine-and nicotine-related behaviors (Balda et al, 2006;Kerstetter and Kantak, 2007;Shram et al, 2008), as well as fewer signs and symptoms of drug withdrawal among adolescent rodents compared with adults (Doherty and Frantz, 2012b); Doremus et al, 2003;O'Dell et al, 2006;Hodgson et al, 2009).…”

“…Less heroin-related Fos in adolescent prefrontal cortex JM Doherty et al extinction of nicotine-seeking (Shram et al, 2008) and less nicotine-paired cue-conditioning among adolescent vs adult rats (Schochet et al, 2004). Cognitive impairment on an amydgala-dependent task after cocaine intake (but not an orbitofrontal cortex-dependent task) is also less severe in younger rats (Harvey et al, 2009;Kerstetter and Kantak, 2007).…”

The Absence of Blocking Innicotine High-Responders as a Possible Factor in the Development of Nicotine Dependence?

“…The solution was administered using programmed 2-s infusions (Razel Model A; Stamford CT) at appropriate intervals during the conditioning procedure via the implanted jugular catheter. Nicotine dose and administration procedures are consistent with previous studies of nicotine self-administration in rodents [37,38].…”

Delayed extinction and stronger reinstatement of cocaine conditioned place preference in adolescent rats, compared to adults.

“…Extinction of nicotine self-administration was found to be shorter in adolescents (Shram, Funk, Li, & Le, 2007), which points again to distinctions in what different behavioral assays measure. It appears from the present data that the association between cocaine and cocaine-paired environments is retained longer in adolescents, compared to adults.…”