Periadolescent nicotine exposure causes heterologous sensitization to cocaine reinforcement

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.…”

Nicotine increases FosB expression within a subset of reward- and memory-related brain regions during both peri- and post-adolescence

“…These changes support prior results implicating involvement of nucleus accumbens in behavioral changes related to drug abuse and, for the first time, identify nicotine-induced altered gene expression in the granule cell layer of hippocampal dentate gyrus, a brain region involved in learning and memory. Because patterns of persistently induced FosB expression were similar after both peri-and post-adolescent nicotine treatments, increased expression of this transcription factor cannot be directly responsible for the behavioral differences observed after the respective treatment periods, and additional studies are required to establish the physiological basis for the distinct effects of peri-vs post-adolescent nicotine treatments (Adriani et al 2003;James-Walke et al 2007;McMillen et al 2005).…”

“…Nicotine treatment of peri-and post-adolescent rats Nicotine was administered after the treatment plan previously demonstrated to increase cocaine reinforcement (McMillen et al 2005). For periadolescent treatment, replicate experiments employed 16 juvenile SpragueDawley rats (34 days old, purchased at 30 days from Harlan, Frederick, MD, USA).…”

“…In rats, it is clear that periadolescent nicotine treatment produces behavioral changes that last to adulthood. These persistent changes include increased adult self-administration of nicotine that does not occur with post-adolescent treatment (Adriani et al 2003) and increased cocaine and diazepam reinforcement in animals treated with nicotine as periadolescents (JamesWalke et al 2007;McMillen et al 2005). Periadolescent nicotine exposure, consisting of ten single daily IP injections of 0.4 mg/kg from postnatal days 34-43 (roughly periadolescence in this species, Spear 2000), is associated with changes in expression levels of a subset of subunits that comprise nicotinic acetylcholine receptors (Adriani et al 2003) and implicates involvement of altered neurophysiology underlying the phenomenon.…”

“…Because FosB expression is important to drug reward (McClung and Nestler 2003), it is possible that the effects of early nicotine exposure to increase behavioral reinforcement produced by cocaine (McMillen et al 2005) are related to increased FosB expression. We have tested this possibility by measuring densities of FosB-reactive nuclei in relevant brain regions as a function of early nicotine exposure.…”