Rats quit nicotine for a sweet reward following an extensive history of nicotine use

Abstract

Drug use may be exacerbated in environments which lack alternative means of engaging in rewarding behaviour. When alternative rewards are available, drug use may decrease-an effect that can be harnessed for therapeutic benefit. This idea is particularly well-supported by recent preclinical evidence demonstrating that a majority of rats will readily choose a potent non-drug reward over cocaine or heroin. Here we examine whether the same holds true for nicotine, a drug considered to have one of the highest addiction liabilities amongst drugs of abuse. Rats were trained to nose-poke separately for saccharin or nicotine on alternate days. Using a discrete-trial, forced-choice procedure, rats were then allowed to choose between nicotine and saccharin. This was followed by choice testing after a decrease in saccharin concentration (0.2-0%), omission of the fluid reward, an increase in nicotine concentration and following an extended nicotine self-administration history. All rats demonstrated a clear and immediate preference for saccharin at all times. This was despite variations in reward concentrations, or after an extensive nicotine history. Notably, rats preferred to nose-poke for water over nicotine and would omit responses when no fluid was delivered, rather than resume responding for nicotine. Overall, this study confirms and extends to nicotine previous research on other drugs of abuse, including cocaine and heroin. The ease with which rats quit nicotine in the present study contrasts with the well-known difficulty of humans to quit tobacco smoking. Possible factors that could explain this apparent discrepancy are discussed.

The dual orexin receptor antagonist TCS1102 does not affect reinstatement of nicotine-seeking

“…However, in our protocol rats never associated their operant responses with obtaining food and only ever associated the context of the operant chamber with nicotine rewards. It has now been shown that rats prefer sweet rewards to nicotine, even after a chronic period of access [41], consistent with findings comparing preferences for natural reinforcers to drug reinforcers like cocaine and heroin [42]. By pre-training rats with food and using an FR5 schedule, it is possible that previous studies have enhanced the salience which animals assign to the context and cues in the operant chamber.…”

Insights from Preclinical Choice Models on Treating Drug Addiction

“…To date, preclinical drug versus nondrug choice procedures have been established for the abused drugs cocaine [20–22], methamphetamine [23,24], 3,4-methylenedioxymethamphetamine [25], heroin [26,27], remifentanil [28], secobarbital and chlordiazepoxide [29], and nicotine [30] in either nonhuman primates or rats. With the exception of one heroin versus electrical brain stimulation choice study [31], all other preclinical drug versus nondrug choice procedures have used some food variant as the alternative nondrug reinforcer.…”

“…Lastly, these results show that simply introducing an alternative nondrug reinforcer attenuates the potency of abused drugs to function as reinforcers compared with their potency in other drug self-administration procedures that do not include a concurrently available alternative reinforcer. Furthermore, in the case of the noncaloric sweetener saccharin, the availability of a nondrug reinforcer may attenuate the relative reinforcing efficacy of drugs in a subset of rats [24,30,39]. As described in more detail below, this potency shift may be particularly relevant in the evaluation of candidate pharmacotherapies for substance-use disorders in preclinical drug self-administration procedures.…”

Essential values of cocaine and non‐drug alternatives predict the choice between them

“…Recently, there has been much interest in studying rats’ choice of drug reinforcers over non-drug alternatives (Augier et al 2012; Cantin et al 2010; Caprioli et al 2015; Huynh et al 2015; Kerstetter & Kippin, 2011; Kerstetter et al 2012; Lenoir et al 2013; Madsen & Ahmed, 2015; Panlilio et al 2015; Perry et al 2013, 2015; Thomsen et al 2013; Tunstall & Kearns, 2013, 2014, 2015; Tunstall et al 2014; Vandaele et al 2016; Vanhille et al 2015). This interest has been stimulated by the observation that rats’ choice of drug over non-drug reinforcers more closely approximates addiction-like behavior than self-administration in the absence of alternatives (Ahmed, 2010).…”