Neural substrates of cocaine-cue associations that trigger relapse
Section snippets
Conditioned cues and relapse to drugs of abuse
Drug dependence is characterized by high rates of relapse to drug-seeking and drug-taking behavior following periods of abstinence and drug detoxification. While multiple trigger factors can initiate or sustain relapse, evidence has clearly established the ability of drug-associated environmental cues (e.g., associated drug paraphernalia or locations where a drug was previously consumed) to elicit drug craving, and consequently reinstate drug-seeking and drug-taking. Conditioned-cued responses
Animal models of conditioned-cued relapse
Craving as an operationally defined construct presents a major challenge to establish and measure using animal models of addiction (Littleton, 2000, Markou et al., 1993). However, animal models can clearly provide a variety of objective and quantifiable indices of drug-seeking behavior. The well established self-administration paradigm in laboratory animals (Weeks, 1962) has provided an empirical model to study multiple factors in drug-taking behavior, particularly in regards to the acquisition
Associative learning with drugs of abuse
Chronic drug self-administration involves multiple exposures to the drug-taking environment and all of the specific stimuli associated with the drug-taking experience over periods of days to weeks. Thus, there has been limited focus on the specific phases of drug-stimulus learning. In contrast, a number of animal models of aversive conditioning have extensively examined the separate mnemonic processes of acquisition, consolidation, and expression of discrete conditioned associations (Davis et
Neural substrates of drug-cue associations
Several lines of research have extensively implicated the amygdala in the acquisition and expression of a variety of motivational tasks, both aversive (Cahill and McGaugh, 1990, LeDoux, 2000) and appetitive (Everitt et al., 2000, Gallagher and Chiba, 1996). In our initial studies, we focused extensively on the role of the basolateral complex of the amygdala in reinstatement using animals with an extensive history of drug-cue pairings (i.e., each day of drug self-administration included discrete
Extending the circuitry of drug-cue associations
Most of our previous work using the reinstatement model of relapse has focused on amygdalar mediation of drug-stimulus associative learning that contributes to reinstatement of drug-seeking behavior. The amygdala has widespread connections with a number of forebrain structures, including extensive glutamatergic efferent projections to the nucleus accumbens and prefrontal cortex (Brinley-Reed et al., 1995, McDonald, 1991, Sesack et al., 1989). In regards to the expression of reinstatement, we
Acknowledgement
The authors' work is supported by the National Institute on Drug Abuse (DA10462, DA15369, DA16511).
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