Nicotine Self-Administration in Animals: A Reevaluation

Abstract

Nicotine self-administration in animals is often viewed as compelling evidence that nicotine is reinforcing to animals and as corroborating the widely accepted thesis that nicotine is a major cause of smoking. This review examines the studies of nicotine self-administration in animals in the past two decades, focusing on threats to the internal and external validity of these studies and on the extent to which they support the thesis that nicotine is reinforcing in animals. The review shows that nicotine self-administration studies are fraught with severe methodological problems. These include omission of essential controls for general activation and other systemic effects of nicotine, insufficient consideration of secondary reinforcement processes, using food-deprived or confined animals and exclusion of subjects that do not conform to the investigators' preferred behavior. As a result of these systematic flaws, the role of nicotine as a reinforcer in this paradigm has not been established.

Reward potentiation or behavioral activation? A comment on Donny et al.

“…Hence, given their current position that the VS is a primary reinforcement, the statement that nicotine self-administration in the above study was dependent on it being response-contingent "in the absence of other reinforcing stimuli" is inexplicable. Just as puzzling is the authors' claim, based on the same study, that nicotine at a dose of 0.03 mg/kg only increases self-administration when contingent on lever press, which is a finding the authors themselves failed to replicate, both in the present study and in a previous one (Donny et al 2000; see discussion in Dar and Frenk 2002).…”

“…The possibility that light may act as an unconditional reinforcement in nicotine self-administration studies was explicitly discussed in our critique of the nicotine addiction thesis (Frenk and Dar 2000, p. 62) and again in our review of animal self-administration studies (Dar and Frenk 2002). [Incidentally, as Donny and one of his co-authors for the present article reviewed our book (Donny et al 2002), their failure to cite it is puzzling.]…”

“…As we have argued elsewhere (Frenk and Dar 2000;Dar and Frenk 2002), however, in this paradigm the inactive lever is not an appropriate control for general activation. In this study, as in others using the same paradigm, animals were trained to lever-press on the active lever using food reinforcement, whereas pressing on the inactive lever was never reinforced.…”

Reevaluating the nicotine delivery kinetics hypothesis

“…However, a separate experiment in which nicotine was administered to the monkeys at the same speeds used in the self-administration procedures showed that infusion speed and plasma nicotine levels were highly correlated (r=0.74; p<0.01). As higher blood levels of nicotine can lead to increased level pressing because of general activation (Dar and Frenk 2002), this confound undermines the attribution of increased level pressing to reinforcement by fast delivery of nicotine. West et al (2000) compared the abuse liability and dependence potential of four NRTs as follows: nicotine gum, patch, spray, and inhaler.…”

Multiple effects of nicotine on behavior: a reply to Frenk and Dar (2003)

“…Here, we highlight some of the evidence for our hypothesis and explain why behavioral activation does not adequately account for the available data. Before presenting these data, we want to identify clearly the alternative hypothesis Frenk and Dar are proposing Dar 2000, 2003;Dar and Frenk 2002). They suggest that lever pressing is a consequence of prior food training and/or non-drug stimuli that either act as unconditioned reinforcers, or conditioned reinforcers (as a consequence of their pairing with food).…”