Age-dependent effects of low-dose nicotine treatment on cocaine-induced behavioral plasticity in rats

Abstract

Rationale Epidemiological evidence of early adolescent tobacco use, prior to that of marijuana and other illicit drugs, has led to the hypothesis that nicotine is a "gateway" drug that sensitizes reward pathways to the addictive effects of other psychostimulants. Objective To test this hypothesis, we have compared the effect of a brief, low-dose nicotine pretreatment of adolescent and adult rats on subsequent locomotor response to acute and chronic cocaine. Materials and methods Adolescents, aged postnatal day (P) 28, and adults, aged P86, were given four daily injections of saline or nicotine (0.06 mg/kg, i.v.). At P32 and P90, rats were given acute injections of cocaine (0, 0.4 or 1.0 mg/kg, i.v.) and monitored for locomotor activity in either a habituated or novel test environment. To examine cocaine sensitization, rats were treated for 3 days with saline or cocaine (0.4 mg/kg, i.v.), and, after 1 day of withdrawal, were given a challenge dose of cocaine (0.4 mg/kg, i.v.). Results Nicotine pretreatment did not affect acute, druginduced locomotor activity at either age. However, age differences in cocaine response were observed, with adolescent animals showing enhanced locomotor activity in the novel environment. Adolescent controls did not exhibit cocaine-induced locomotor sensitization, whereas adults did. Nicotine pretreatment during adolescence promoted the development and expression of a sensitized response to repeated cocaine exposure similar to that observed in saline-pretreated adult controls. Conclusions These findings show that brief pretreatment with nicotine, in a low dose comparable to that inhaled in 2-4 cigarettes, enhances cocaine-induced behavioral plasticity in adolescent rats.

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).…”

“…Indeed, previous studies have shown that nicotine exposure during adolescence period alter the aversive (Hutchison and Riley, 2008) and rewarding (Kelley and Rowan, 2004;Schochet et al, 2004) effects of cocaine. Although an earlier study reported that prior nicotine treatment only enhanced the rewarding action of cocaine in adolescents but not adult rats (McQuown et al, 2009;Mojica et al, 2014), limited information is available on the impact of nicotine exposure during adulthood on cocaine reward, extinction and reinstatement in mice.…”

“…Research in the past has shown that nicotine use is initiated during adolescent period and proceeds to the use and abuse of other drugs (Best et al, 2000;Businelle et al, 2013;Carmody et al, 1985;DiFranza and Guerrera, 1990;Lisha et al, 2014;McKee et al, 2011;Rimm et al, 1995;Romberger and Grant, 2004;Torabi et al, 1993;York and Hirsch, 1995). 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;…”

“…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).…”

D1/D5 receptors and histone deacetylation mediate the Gateway Effect of LTP in hippocampal dentate gyrus

“…Thus, nicotine can serve as a "gateway" drug that may lead to a change in the rewarding effect of other drugs, such as cocaine. Behavioral studies in rodents indicated that prior exposure to nicotine produces a greater increase in selfadministration, sensitization, and conditioned place preference than the administration of cocaine alone (Klein 2001;Desai and Terry 2003;Collins et al 2004;McMillen et al 2005;McQuown et al 2009;Levine et al 2011;Mello and Newman 2011). However, the molecular and synaptic mechanisms underlying this gateway effect are not completely understood.…”