Low dose nicotine treatment during early adolescence increases subsequent cocaine reward

Abstract

Adolescence is a critical period for the initiation of drug use, starting with tobacco and alcohol and progressing to marijuana and other illicit drugs. These findings have led to the suggestion that tobacco and alcohol are 'gateway' drugs that sensitize maturing reward pathways to the effects of illicit substances such as cocaine. To test this hypothesis, we have examined whether low-dose nicotine pretreatment alters acquisition of cocaine self-administration in adolescents more than in adults. Male and female Sprague-Dawley rats, aged postnatal day (P) 28 or P86, were given two daily intravenous injections of nicotine (0.03 mg/kg/0.1 ml) or saline for four days. At P32 and P90, rats were placed in self-administration chambers and tested for acquisition of cocaine (0.2 or 0.5 mg/kg/inj) for five days. Data were collapsed across cocaine dose and sex since there was no significant effect of these variables. Adolescent rats pretreated with nicotine exhibited significantly greater cocaine-reinforced responding as compared to saline controls or adults (p < 0.01). This drug pretreatment effect did not generalize to all rewards, since nicotine did not increase responding for sucrose pellets in adolescents. These findings provide evidence that the adolescent brain is uniquely vulnerable to the effects of nicotine on subsequent drug reward.

Nicotine pretreatment reduced cocaine-induced CPP and its reinstatement in a sex- and dose-related manner in adult C57BL/6J mice

“…Likewise, reinstatement of CPP was not altered in mice pretreated with the higher dose of nicotine. Our results are consistent with previous studies in rats showing that nicotine pretreatment increased cocaine-induced reinforcement (McQuown et al, 2007) as well as locomotor sensitization (McQuown et al, 2009) in adolescent but not adult rats. Interestingly, nicotine withdrawal has been shown to differentially regulate extracellular levels of accumbal dopamine in adolescent versus adult rats (Natividad et al, 2010).…”

“…This period of life is a very sensitive age in which the negative affective state associated with nicotine withdrawal is reduced while the rewarding action of nicotine is enhanced compared to adults (Carcoba et al, 2014;Dickson et al, 2014;Dickson et al, 2011;Hutchison and Riley, 2008;Lee et al, 2015;McQuown et al, 2009;Natividad et al, 2012;Natividad et al, 2010;Natividad et al, 2013;O'Dell et al, 2004;O'Dell et al, 2006;O'Dell et al, 2007;Shram et al, 2008;Torres et al, 2008;Wilmouth and Spear, 2004), making adolescents a vulnerable target to nicotine use and abuse as well as for use of other addictive drugs during adulthood. Consistent with this notion, previous studies have shown that nicotine exposure during adolescence can prime the use and abuse of cocaine, alcohol, and other addictive substances (Bechtholt and Mark, 2002;DiFranza and Guerrera, 1990;Horger et al, 1992;Hutchison and Riley, 2008;Kandel and Kandel, 2015;Kandel and Kandel, 2014;Kelley and Rowan, 2004;Kouri et al, 2001;Levine et al, 2011;Li et al, 2014;McQuown et al, 2007;McQuown et al, 2009;Meliska et al, 1995;Natividad et al, 2010;Rinker et al, 2011;Rosenberg, 2014;Schindler et al, 2012;Schneider et al, 2012). There is also evidence showing that about 90% of regular smokers start using tobacco at an early age, and that early onset smoking carries a major risk for the development of addiction to other drugs of abuse (Rimm et al, 1995).…”

“…Many studies have reported that nicotine may serve as a gateway drug for cocaine and other illicit drugs (Dickson et al, 2014;Dickson et al, 2011;Levine et al, 2011;Li et al, 2014;McQuown et al, 2007;Orsini et al, 2008). However, there is limited information on the effect of nicotine treatment on the rewarding action of cocaine if nicotine is administered during adulthood.…”

“…For example, previous studies have shown that nicotine exposure during adolescence can pave the way to the use and abuse of cocaine, alcohol, and other addictive substances (Levine et al, 2011;McQuown et al, 2007;Orsini et al, 2008). Interestingly, an epidemiological study has shown that, just alone in the United States, 90.4% of adults (between the ages of 18-34), who had used cocaine at least once had also smoked cigarettes before (Levine et al, 2011).…”

“…Many preclinical studies have also demonstrated the effect of early nicotine use on the reinforcing and rewarding effects of cocaine. For instance, pretreatment with nicotine has been shown to facilitate cocaine self-administration (McQuown et al, 2007), cocaine-induced reward (Li et al, 2014) and locomotor sensitization (Kandel and Kandel, 2014). Additionally, pretreatment with nicotine (0.32 mg/kg) produced a leftward shift in the cocaine's dose-response curve in Rhesus monkeys (Mello and Newman, 2011).…”