Effects of simultaneous exposure to stress and nicotine on nicotine-induced locomotor activation in adolescent and adult rats

Abstract

Preclinical studies have shown that repeated stress experiences can result in an increase in the locomotor response to the subsequent administration of drugs of abuse, a phenomenon that has been termed behavioral cross-sensitization. Behavioral sensitization reflects neuroadaptive processes associated with drug addiction and drug-induced psychosis. Although crosssensitization between stress- and drug-induced locomotor activity has been clearly demonstrated in adult rats, few studies have evaluated this phenomenon in adolescent rats. In the present study, we determined if the simultaneous exposure to stress and nicotine was capable of inducing behavioral sensitization to nicotine in adolescent and adult rats. To this end, adolescent (postnatal day (P) 28-37) and adult (P60-67) rats received nicotine (0.4 mg/kg, sc) or saline (0.9% NaCl, sc) and were immediately subjected to restraint stress for 2 h once a day for 7 days. The control group for stress was undisturbed following nicotine or saline injections. Three days after the last exposure to stress and nicotine, rats were challenged with a single dose of nicotine (0.4 mg/kg, sc) or saline and nicotine-induced locomotion was then recorded for 30 min. In adolescent rats, nicotine caused behavioral sensitization only in animals that were simultaneously exposed to stress, while in adult rats nicotine promoted sensitization independently of stress exposure. These findings demonstrate that adolescent rats are more vulnerable to the effects of stress on behavioral sensitization to nicotine than adult rats.

Restraint stress attenuates nicotine's locomotor stimulant but not discriminative stimulus effects in rats

“…Effects of sequential exposure to stress and nicotine were not studied. It is difficult to compare these findings with ours given the substantial methodological differences across studies (e.g., nicotine’s locomotor effects in Zago et al (2012) were only measured 3 days after completion of the nicotine/stress regimen). Nonetheless, together these studies support the utility of using simultaneous stress procedures to understand the role of stress in drug addiction.…”

“…In the only other study to evaluate the effects of simultaneous stress exposure on drug-induced locomotor activity, a history of repeated exposure to nicotine and simultaneous restraint stress enhanced nicotine’s acute locomotor stimulant effects in adolescent but not adult rats (Zago et al, 2012). Effects of sequential exposure to stress and nicotine were not studied.…”

“…While this approach has been very valuable, humans may also be exposed to stress and drugs simultaneously rather than sequentially (e.g., smoking in the presence of social stress). Models involving the use of simultaneous exposure to stress and drugs may therefore provide additional insights into the role of stress in addiction (see Zago et al, 2012). In addition, duration of the interval between stress and drug administration can influence magnitude of stress effects on drug-induced locomotor stimulation (e.g., Stohr et al, 1999; Vanderschuren et al, 1997).…”

Tabagismo: o que tem sido abordado em periódicos brasileiros

“…However, the study did not show cross-sensitization, suggesting that the MPH treatment did not induce neuroadaptation in rats that could increase sensitivity to nicotine. In a similar study, also in rats, but evaluating the use of stress as a possible sensitizer factor to nicotine, Zago et al 54 verified that in adolescent rats, nicotine caused behavioral sensitization only in those that were exposed simultaneously to stress, whereas in adult rats, nicotine promoted sensitization regardless of exposure to stress. Manzano et al 55 , in an experimental study in humans that assessed 25 young smokers, verified a decrease in the indicators of heart rate variability after having smoked two cigarettes after an interval of 8 hours of abstinence, with recovery values after 30 minutes, showing acute effect of exposure and confirming the findings of other studies, as demonstrated in a newly published review 56 .…”

Emergence of sex differences in the development of substance use and abuse during adolescence

“…One factor might be that drugs which rely on dopamine release like amphetamine and methylphenidate may be less effective than drugs that inhibit uptake like cocaine due to the relative lack of stores to mobilize in adolescents compared to adults (Walker et al, 2010). However, similarly disparate findings are reported for nicotine, with one study reporting a sensitization that perseveres to adulthood (Faraday et al, 2003), another which reported sensitization in adults but not adolescents (Zago et al, 2012), and a third which reported comparable sensitization following adolescent or adult treatment (Adriani, Deroche-Gamonet, Le Moal, Laviola, & Piazza, 2006) Two studies reported increased cross-sensitization to cocaine (Santos, Marin, Cruz, Delucia, & Planeta, 2009) or amphetamine (McQuown et al, 2009) after adolescent nicotine. Similarly, one study reported comparable sensitization to heroin in adolescents and adults (Doherty & Frantz, 2013), while another reported more persevering sensitization in adolescents than adults (Koek, 2014).…”