Are Cocaine-Seeking “Habits” Necessary for the Development of Addiction-Like Behavior in Rats?

Abstract

Drug self-administration models of addiction typically require animals to make the same response (e.g., a lever-press or nose-poke) over and over to procure and take drugs. By their design, such procedures often produce behavior controlled by stimulus-response (S-R) habits. This has supported the notion of addiction as a "drug habit," and has led to considerable advances in our understanding of the neurobiological basis of such behavior. However, to procure such drugs as cocaine, addicts often require considerable ingenuity and flexibility in seeking behavior, which, by definition, precludes the development of habits. To better model drug-seeking behavior in addicts, we first developed a novel cocaine self-administration procedure [puzzle self-administration procedure (PSAP)] that required rats to solve a new puzzle every day to gain access to cocaine, which they then self-administered on an intermittent access (IntA) schedule. Such daily problem-solving precluded the development of S-R seeking habits. We then asked whether prolonged PSAP/IntA experience would nevertheless produce "symptoms of addiction." It did, including escalation of intake, sensitized motivation for drug, continued drug use in the face of adverse consequences, and very robust cue-induced reinstatement of drug seeking, especially in a subset of "addiction-prone" rats. Furthermore, drug-seeking behavior continued to require dopamine neurotransmission in the core of the nucleus accumbens (but not the dorsolateral striatum). We conclude that the development of S-R seeking habits is not necessary for the development of cocaine addiction-like behavior in rats. Substance-use disorders are often characterized as "habitual" behaviors aimed at obtaining and administering drugs. Although the actions involved in consuming drugs may involve a rigid repertoire of habitual behaviors, evidence suggests that addicts must be very creative and flexible when trying to procure drugs, and thus drug seeking cannot be governed by habit alone. We modeled flexible drug-seeking behavior in rats by requiring animals to solve daily puzzles to gain access to cocaine. We find that habitual drug-seeking isn't necessary for the development of addiction-like behavior, and that our procedure doesn't result in transfer of dopaminergic control from the ventral to dorsal striatum. This approach may prove useful in studying changes in neuropsychological function that promote the transition to addiction.

Incentive and dopamine sensitization produced by intermittent but not long access cocaine self‐administration

“…Finally, LgA rats had higher Q 0 than IntA rats after prolonged self-administration (effect of group, p = 0.03). These differential effects of LgA and IntA on Q 0 are consistent with several reports (Bentzley et al, 2014;James et al, 2018;Kawa et al, 2016;Oleson & Roberts, 2009;Singer, Fadanelli, Kawa, & Robinson, 2018).…”

“…In contrast, Q 0 did not correlate with [DA] when all groups were combined (R 2 = 0.07, p = 0.17; Figure 6c) or within any individual group (all p-values >0.1). IntA experience reliably produces multiple addictionlike behaviors and this has been shown to be particularly robust in susceptible individuals (Kawa et al, 2016;Singer et al, 2018). In an effort to quantify this variation in behavior, we developed an "IntA Addiction Score", similar to the oft-used addiction-criteria analysis (Deroche-Gamonet et al, 2004;Kawa et al, 2016;Singer et al, 2018), but differing in the behaviors that were analyzed.…”

Intact goal‐directed control in treatment‐seeking drug users indexed by outcome‐devaluation and Pavlovian to instrumental transfer: critique of habit theory

“…Thus, drug users' failure to demonstrate impaired goal-directed control in the current choice designs could be taken as positive evidence that drug users have no such impairment. Finally, if habitual control was limited to situations in which there is only one choice, then the animal model would lack ecological validity for complex human environments in which multiple choices are on offer (Heather, 2017;Singer et al, 2018).…”

Are animal models of addiction useful?

“…). We agree that sophisticated animal models that incorporate social factors, problem‐solving and a choice of reinforcers should increase the relevance of animal models of addiction to the human condition . However, given its complex nature, we consider it unlikely that animal models will ever be able to model the relations between subjective symptoms and the economic and social factors that determine the onset and persistence of addiction (and recovery from it) in humans.…”

“…Another recently developed animal drug self-administration paradigm also questions the importance of habitual and inflexible behaviour in the development of addiction. Building on observations of the extent of planning and problem solving reported by human addicts in order to obtain drugs [32], Singer et al [45] developed a novel cocaine self-administration procedure that required rats to solve puzzles in order to obtain access to cocaine. The rats were required to solve different puzzles each time, which prevented drug-seeking from becoming habitual and inflexible.…”