Are cocaine-seeking “habits” necessary for the development of addiction-like behavior in rats?

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, for addicts to procure drugs, like cocaine, often requires 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 (the 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