Tobacco smoke and ethanol during adolescence: Both combined- and single-drug exposures lead to short- and long-term disruption of the serotonergic system in the mouse brain.

The impairment of the serotonergic system contributes to nicotine and ethanol effects on mood, suggesting that this system is targeted by each of these drugs and that co-exposure possibly worsens the disruption. Here, we tested this hypothesis in an adolescent mice model of tobacco smoke and/or ethanol exposure. From postnatal day (PN) 30-45, Swiss mice were exposed to one of the following: 1) tobacco smoke (SMK; research cigarettes 2R1F, whole-body exposure, 8 h/daily); 2) ethanol (ETOH; 2 g/kg i.p., every other day); 3) SMK + ETOH; 4) Control (VEH). At PN45 (end-of-exposure), hippocampal serotonin transporter (5 H TT) binding was increased in SMK and decreased in ETOH male mice. At PN50 (short-term deprivation), cortical 5 H TT was reduced in all drug-exposed mice. In the hippocampus, similar deficits were identified in females. In both brain regions, the effects of SMK + ETOH deprivation on 5 H TT were equivalent to the damage caused by either drug. At PN50, hippocampal 5 H T1A receptor binding was reduced in ETOH and SMK + ETOH mice. Similar results were observed in the male cortex. In females, deficits were identified in SMK mice. In both brain regions, SMK + ETOH 5 H T1A deficits reflected the summation of SMK and ETOH outcomes. At PN75 (long-term deprivation), there was a late-emergent increase in cortical 5 H T1A binding in SMK mice, while cortical 5 H T2 receptor binding was similarly increased in SMK and SMK + ETOH groups. Adolescent SMK and/or ETOH serotonergic impairment is sex-dependent and most evident during short-term deprivation. SMK + ETOH deprivation evokes serotonergic disruption that is at least equivalent to that caused by either drug alone.

Maternal undernutrition during lactation alters nicotine reward and DOPAC/dopamine ratio in cerebral cortex in adolescent mice, but does not affect nicotine-induced nAChRs upregulation.

Early undernutrition causes long lasting alterations that affect the response to psychoactive drugs. Particularly, undernutrition during lactation affects the acute locomotor response to nicotine during adolescence, but the reward effect of continued exposure to nicotine remains unknown. The goal of this study was to investigate the effects of undernutrition during lactation on the nicotine susceptibility indexed via conditioned place preference (CPP), on dopamine content and turnover and on nicotine-induced nicotinic cholinergic receptor (nAChR) upregulation in the cerebral cortex, midbrain and hippocampus of adolescent mice. The impact of undernutrition and nicotine exposure on stress-related hormones and leptin was also investigated. From postnatal day 2 (PN2) to weaning (PN21), dams were randomly assigned to one of the following groups: Control (C) - free access to standard laboratory diet (23% protein); Protein Restricted (PR) - free access to isoenergenetic diet (8% protein); Calorie Restricted (CR) - access to standard laboratory diet in restricted quantities (mean ingestion of PR). PR and CR groups showed less mass gain and less visceral fat mass. While C and CR were equally susceptible to nicotine-induced place preference conditioning, PR failed to show a conditioning pattern. In contrast, all groups presented a nicotine-evoked nAChR upregulation in the cerebral cortex. While dopamine and DOPAC levels did not differ between groups, the DOPAC/dopamine ratio was increased in CR animals. No differences in endocrine parameters were observed. Taken together, our results indicate that undernutrition during lactation programs for brain alterations later in life. Our data also suggest that early undernutrition does not affect the rewarding associative properties of nicotine at adolescence.