Kicking the habit: The neural basis of ingrained behaviors in cocaine addiction

Abstract

Cocaine addiction is a complex and multifaceted process encompassing a number of forms of behavioral plasticity. The process of acquiring and consuming drugs can be sufficiently risky and complicated that the casual drug user may choose not to act on every motivation to use drugs. The repetition of drug seeking and taking, however, often results in the gradual development of drug craving and compulsive drug seeking associated with addiction. Moreover, the complex sets of behaviors associated with drug addiction can become ingrained to such an extent that, when activated by drug-associated stimuli or exposure to the drug itself, the processes underlying drug seeking and taking are automatically engaged and very difficult to suppress. Here, we examine the hypothesis that aspects of cocaine seeking and taking become ingrained with repetition, thereby contributing to continued drug use despite a conscious desire to abstain. We also review emerging evidence indicating that neuronal circuits including the dorsolateral striatum play a particularly important role in the habitual aspects of drug seeking and taking.

Compulsive drug use and its neural substrates

“…On the basis of the pioneering studies by Di Chiara and colleagues in the 1980s that showed that different drugs abused by humans all increase dopamine release within the nucleus accumbens (Di Chiara and Imperato, 1988), numerous pharmacological and molecular studies have substantiated the involvement of the ventral striatum in self-administration of different classes of abused drugs (Ikemoto and Wise, 2004;Pierce and Kumaresan, 2006). More recently, habit-based theories of addiction (Tiffany, 1990;Everitt et al, 1999;Everitt and Robbins, 2005;Pierce and Vanderschuren, 2010) have inspired work on the role of the dorsal striatum in drug use and addiction.…”

“…How the deficit in NMDA-receptor-dependent long-term depression in the nucleus accumbens core contributes to the behavioral signs of addiction remains to be demonstrated. Studies focusing on the role of cocaine-associated stimuli in drug seeking and taking have indicated that the nucleus accumbens core might provide a gateway by which dorsal striatal mechanisms gain control over behavior, perhaps associated with habitual forms of drug seeking and taking (Everitt and Robbins, 2005;Pierce and Vanderschuren, 2010). These findings are buttressed by converging lines of evidence.…”

“…The last 5 decades have seen enormous progress in our knowledge of the neural underpinnings of the rewarding and motivational properties of drugs of abuse (e.g., Wise, 1996;Van Ree et al, 1999;Everitt and Robbins, 2005;Pierce and Kumaresan, 2006;Spanagel, 2009;Koob and Volkow, 2010). However, we are only beginning to understand the neurobiological mechanisms that underlie the genuine of loss of control over drug use that characterizes drug addiction (and contrasts it from mere drug use) (Everitt and Robbins, 2005;Kalivas and Volkow, 2005;Kenny, 2007;Koob and Volkow, 2010;Pierce and Vanderschuren, 2010;Ahmed, 2012). Quite clearly, it is not unreasonable to expect that advancing our insight into the neural underpinnings of addictive behavior may contribute to the development of better therapies that target the core of this devastating disorder.…”

Towards an Animal Model of Food Addiction

“…Likewise, it has been shown that the neural response to a methylphenidate challenge differs between cocaine addicts and control subjects [145]. Since the development of addictive behavior relies on concerted neural changes in the VTA, the striatum, the amygdala, and the PFC [44,146], these circuits should be investigated accordingly.…”

Differential expression of Arc in the mesocorticolimbic system is involved in drug and natural rewarding behavior in rats

“…The dorsomedial striatum (DMS), which receives input primarily from the prefrontal cortex [3] , appears to be preferentially involved in the rapid acquisition of actionoutcome behavior [4,5] and is thought to contribute to the early performance of drug-seeking behavior. By contrast, the lateral striatum, which receives input from the sensorimotor cortex [3] , is critical for the acquisition of stimulus-response habitual behavior [4,6] and is thought to be involved in cue-controlled forms of addictive behavior after extensive drug-taking experience [7,8] . The lateral striatum is also involved in the reinstatement of drug seeking after protracted withdrawal and in relapse to a drug-seeking state [9,10] .…”