Prenatal nicotine exposure changes natural and drug‐induced reinforcement in adolescent male rats

Abstract

Clinical studies have demonstrated an increased incidence of substance misuse and obesity in adolescents whose mothers smoked during pregnancy. Although dopamine systems that mediate natural and drug-induced reinforcement have been shown in animal studies to be altered by gestational nicotine treatment, it is not clear whether there are concomitant changes in reinforcement sensitivity. To test whether prenatal nicotine exposure influences sensitivity to natural and drug rewards, timed pregnant rats were implanted with osmotic minipumps delivering saline or nicotine (3 mg/kg/day) from gestational day 4 to 18. Male offspring were tested as adolescents, on postnatal day 32, for operant responding maintained by sucrose pellets or i.v. cocaine (200 or 500 mug/kg per injection). Cocaine-induced stereotypy and c-fos mRNA expression in cortex and striatum were also examined. Complex changes in reward circuitry were observed in the offspring of nicotine-exposed dams. Nicotine-exposed adolescents did not self-administer the low dose of cocaine, but, at the higher dose, exhibited significantly greater cocaine intake and c-fos mRNA expression in nucleus accumbens than did controls. In contrast, control animals showed significantly greater drug-induced stereotypy at both cocaine doses. Operant responding maintained by sucrose was also influenced by gestational nicotine exposure. At a fixed ratio (FR) 1 schedule, although the number of pellets eaten by the two experimental groups was equivalent, more pellets were left uneaten by nicotine-exposed offspring. At FR2 and FR5 schedules, the responding maintained by sucrose pellets was lower in nicotine-exposed offspring. These findings suggest that nicotine exposure during gestation may induce changes in both natural and drug reward pathways.

Maternal nicotine exposure during lactation alters food preference, anxiety-like behavior and the brain dopaminergic reward system in the adult rat offspring

“…In addition, studies have shown an association between gestational tobacco smoke exposure and increased consumption of palatable foods by the offspring both in humans [5] and rats [42]. Indeed, adult rats chronically exposed to nicotine eat greater amounts of sucrose [55].…”

“…Studies using nicotine alone have been used to assess possible associations between smoking and neurobehavioral changes [28,42,100,110]. Since nicotine is considered the main psychoactive component of tobacco smoke that causes dependence [18,27], experimental models based on nicotine exposure during development should be useful to study the short-and long-term behavioral consequences of early tobacco smoke exposure ( [4],; [3,69]).…”

Saguenay Youth Study: A multi-generational approach to studying virtual trajectories of the brain and cardio-metabolic health

“…Although observational studies cannot attribute solely such associations to MSP (D'Onofrio et al, 2012), human studies with genetically sensitive research designs (Gaysina et al, 2013) and preclinical studies of prenatal exposure to nicotine (Franke et al, 2008) suggest that these prenatal exposures do play a role in shaping mentalhealth trajectories. Furthermore, careful consideration of potential confounders, such as maternal education and alcohol use during pregnancy, when examining the relations between externalizing behavior and substance use (Lotfipour et al, 2014) or the specificity of some of the observed structure-function relationships (e.g., correlation between the amygdala volume with fat preference but not with alcohol use; Haghighi et al, 2013) suggest that these associations are not due to global phenomena (such as "poverty" or an "addictive personality" of the parents).…”

Effects of Pre- and Neonatal Nicotine Exposure in Rodents: Inconsistent Evidence

“…Prenatal nicotine administration leads to increased depressive behaviors as measured by learned helplessness, fear trace conditioning (Paz et al 2007), and anhedonia (Franke et al 2008). The decrease in anxiety-like behavior, as measured with the elevated plus maze, has been interpreted as indicative of increased risk-taking behavior (Ajarem and Ahmad 1998;Sobrian et al 2003).…”

“…(C1) King and Strand 1988;LeSage et al 2006;Pauly et al 2004;Peters and Tang 1982;Schlumpf et al 1988;Vaglenova et al 2004. forcement schedules (Franke et al 2008;Martin and Becker 1971). The conditioned avoidance response (CAR) involves intermediate complex association ability.…”