Effects of acute and repeated nicotine administration on delay discounting in Lewis and Fischer 344 rats

Abstract

Biological differences may underlie individual differences in impulsive behavior, such as choice for a smaller, more immediate reinforcer over a larger, more delayed reinforcer. Repeated exposure to drugs of abuse may have differing effects on such behavior. To evaluate acute and repeated effects of nicotine on impulsive choice, two strains of rats that have been shown to differ in impulsive choice were tested in a delay-discounting paradigm. Eight Lewis and eight Fischer 344 rats were allowed to choose between one food pellet delivered immediately and three food pellets delivered after a delay. The delay systematically increased in blocks of trials within each session, and the delay value at which choice for the two alternatives was equal (i.e., the indifference point) was interpolated. Effects of nicotine (0.1 – 1.0 mg/kg, s.c.) on percent choice and indifference points were determined during the acute-testing phase and during the re-determination of effects of each dose following at least 30 sessions of repeated 1.0 mg/kg nicotine exposure. Lewis rats had shorter indifference points (i.e., made fewer larger reinforcer choices) than the Fischer 344 rats. Acute nicotine administration increased mean larger-reinforcer choices at the 0.3 mg/kg dose in the Lewis rats and at the 1.0 mg/kg dose in the Fischer 344 rats. After repeated exposure to nicotine, indifference points returned to near baseline (pre-drug) levels for both strains. Strain differences were observed in rates of delay discounting and nicotine may decrease impulsive choice acutely, but this effect does not appear to be long-lasting.

A long-term study of the impulsive choices of Lewis and Fischer 344 rats

“…It could be said that in adjusting to the transition from the ascending to the descending presentation order of delays, the LEWs did so more rapidly than the F344s, choosing the LL lever at higher proportions during most delays to LLR. This result is in dispute with previous findings (Anderson & Diller, 2010;Anderson & Woolverton, 2005;Huskinson et al, 2012;Madden et al, 2008;Stein et al, 2012) that showed more impulsivity in the LEWs; the assertion that the LEWs choose more impulsively than the F344s is not supported by the present study, challenging this strain difference and confirming that it may be due to procedural issues (Stein et al, 2012) and the analytical tools used to characterize impulsive choice (Madden & Johnson, 2010).…”

“…For instance, studies using an autoshaping technique (Brown & Jenkins, 1968) to establish lever pressing for food found that the LEWs acquired that behavior more rapidly and performed it at higher rates than the F344s (Kearns, Gomez-Serrano, Weiss, & Riley, 2006); similar results were documented by Anderson and Elcoro (2007) using a tandem fixed-ratio one, fixed-time 20 s schedule of reinforcement to establish lever pressing for food. Moreover, studies of impulsive choice in LEWs and F344s have shown steeper discounting functions for the former than for the latter strain of rats (e.g., Anderson & Diller, 2010;Anderson & Woolverton, 2005;Huskinson, Krebs, & Anderson, 2012;Madden, Smith, Brewer, Pinkston, & Johnson, 2008). Nonetheless, the generality of this finding has been compromised by research that failed to show differences in discounting functions between LEWs and F344s (e.g., Stein et al, 2012;Wilhelm & Mitchell, 2009).…”

“…Studies using steady-state procedures, arranging a delay/ amount combination for at least ten sessions before replacing it for a different combination, found steeper discount functions in LEWs than in F344s (e.g., Anderson & Diller, 2010;Anderson & Woolverton, 2005;Huskinson et al, 2012;Madden et al, 2008). In contrast, studies that have used a rapid-determination adjusting-amount procedure to control each delay/amount combination in series of five sessions have yielded no differences in discounting functions between LEWs and F344s (Stein et al, 2012;Wilhelm & Mitchell, 2009), suggesting that more than five sessions are required for the rapid-determination adjusting-amount procedure to detect a strain difference that is mainly driven by the LEWs.…”

“…Another objective was to analyze the role of presentation orders of the delays to LLR in determining the slope of the discounting function; this objective is important to ratify the findings of studies with human (e.g., Robles & Vargas, 2007Robles, Vargas, & Bejarano, 2009) and nonhuman (e.g., Fox, Hand, & Reilly, 2008;Slezak & Anderson, 2009) animals showing that the slope of the discounting function is affected by the order in which delays to LLR are presented in the choice situation. The last objective was to compare the impulsive choices of LEWs and F344s, given the growing interest of the scientific community in using these rat strains to assess the effects of drugs and neurobiological variables in determining the slope of the delaydiscounting function; this objective is significant because researchers have suggested that genetic and neurochemical differences between LEWs and F344s account for the dissimilarities in impulsive choice between these inbred rats (e.g., Anderson & Diller, 2010;Garcia-Lecumberri et al, 2011).…”

Time discounting and tobacco smoking: a systematic review and network analysis

“…by inhibiting cortical regulation mechanisms or by impacting the sensitivity of the brain's reward system. 52,78 Previous studies not included in our review found that (i) those seeking smoking cessation had lower discount rates, creating potential selection bias that is unaddressed in experiments analysing voluntary participants, 25 and (ii) timediscounting significantly decreased at a 12-month follow-up among smokers who successfully quit. 79 Conversely, there is also evidence that short-term withdrawal from smoking increases time-discounting.…”