The results suggest that nicotinic enhancement of incentive salience is transient, and a previous history of nicotine use does not cause further sensitization. Taken together, these results suggest that nicotine enhances incentive salience, particularly-and perhaps exclusively-while onboard.

Preclinical studies of nicotine self-administration provide important value for the field as they are highly rigorous, controlled, can be conducted quickly, and are generalizable to humans. Given the translational value of the nicotine self-administration model, and the relatively new guidelines of the National Institutes of Health to include sex as a biological variable, strain and sex differences in nicotine acquisition were examined here in two outbred rat strains. Sprague–Dawley (SD) and Long–Evans (LE; wildtype and cholinergic acetyltransferase cre-recombinase transgenic) rats of each sex were implanted with indwelling intravenous jugular catheters. Rats were trained to self-administer nicotine (0.02 mg/kg per infusion, paired with contingent light + tone stimuli). Acquisition criteria were set at a minimum active:inactive response ratio of 2:1 and a minimum of 10 infusions per session, both of which had to be met for a minimum of 10 sessions. Across 10 sessions, male SD rats self-administered significantly more nicotine than female SD rats (p < .05), indicating a sex difference in this strain. LE females self-administered more nicotine than SD females indicative of a strain difference between females (p < .05). SD males increased nicotine infusions across sessions compared to LE males and SD females (p < .05). No strain or sex differences were observed in the number of sessions to reach criteria. No differences between wildtype and transgenic LE rats were observed. These results demonstrate sex and strain differences in nicotine self-administration between SD and LE rats and may lend insight into development of other nicotine self-administration models, where sex and strain may impact acquisition.

No abstract

Nicotine, the primary addictive substance in tobacco, is widely abused. Relapse to cues associated with nicotine results in increased glutamate release within nucleus accumbens core (NAcore), modifying synaptic plasticity of medium spiny neurons (MSNs) which contributes to reinstatement of nicotine seeking. However, the role of cholinergic interneurons (ChIs) within the NAcore in mediating these neurobehavioral processes is unknown. ChIs represent less than 1% of the accumbens neuronal population and are activated during drug seeking and reward-predicting events. Thus, we hypothesized that ChIs may play a significant role in mediating glutamatergic plasticity that underlies nicotine seeking behavior. Using chemogenetics in transgenic rats expressing Cre under the control of the choline acetyltransferase (ChAT) promoter, ChIs were bi-directionally manipulated prior to cueinduced reinstatement. Following nicotine self-administration and extinction, ChIs were activated or inhibited prior to a cue reinstatement session. Following reinstatement, whole-cell electrophysiology from NAcore MSNs was used to assess changes in plasticity, measured via α-amino-3-hydroxy-5methyl-4-isoxazolepropionic acid (AMPA) / N-Methyl-D-Aspartate (NMDA) (A/N) ratios. Chemogenetic inhibition of ChIs inhibited cued nicotine seeking and resulted in decreased A/N, relative to control animals, whereas activation of ChIs was unaltered, demonstrating that ChI inhibition may modulate plasticity underlying cue-induced nicotine seeking. These results demonstrate that ChI neurons play an important role in mediating cue-induced nicotine reinstatement and underlying synaptic plasticity within the NAcore.

As the genetic bases to variation in anoxia tolerance are poorly understood, we used the Drosophila Genetics Reference Panel (DGRP) to conduct a genome-wide association study (GWAS) of anoxia tolerance in adult and larval Drosophila melanogaster . Survival ranged from 0–100% in adults exposed to 6 h of anoxia and from 20–98% for larvae exposed to 1 h of anoxia. Anoxia tolerance had a broad-sense heritability of 0.552 in adults and 0.433 in larvae. Larval and adult phenotypes were weakly correlated but the anoxia tolerance of adult males and females were strongly correlated. The GWA identified 180 SNPs in adults and 32 SNPs in larvae associated with anoxia tolerance. Gene ontology enrichment analysis indicated that many of the 119 polymorphic genes associated with adult anoxia-tolerance were associated with ionic transport or immune function. In contrast, the 22 polymorphic genes associated with larval anoxia-tolerance were mostly associated with regulation of transcription and DNA replication. RNAi of mapped genes generally supported the hypothesis that disruption of these genes reduces anoxia tolerance. For two ion transport genes, we tested predicted directional and sex-specific effects of SNP alleles on adult anoxia tolerance and found strong support in one case but not the other. Correlating our phenotype to prior DGRP studies suggests that genes affecting anoxia tolerance also influence stress-resistance, immune function and ionic balance. Overall, our results provide evidence for multiple new potential genetic influences on anoxia tolerance and provide additional support for important roles of ion balance and immune processes in determining variation in anoxia tolerance.