The neurocircuitry of addiction: an overview

Abstract

Drug addiction presents as a chronic relapsing disorder characterized by persistent drug-seeking and drug-taking behaviours. Given the significant detrimental effects of this disease both socially and economically, a considerable amount of research has been dedicated to understanding a number of issues in addiction, including behavioural and neuropharmacological factors that contribute to the development, loss of control and persistence of compulsive addictive behaviours. In this review, we will give a broad overview of various theories of addiction, animal models of addiction and relapse, drugs of abuse, and the neurobiology of drug dependence and relapse. Although drugs of abuse possess diverse neuropharmacological profiles, activation of the mesocorticolimbic system, particularly the ventral tegmental area, nucleus accumbens, amygdala and prefrontal cortex via dopaminergic and glutamatergic pathways, constitutes a common pathway by which various drugs of abuse mediate their acute reinforcing effects. However, long-term neuroadaptations in this circuitry likely underlie the transition to drug dependence and cycles of relapse. As further elucidated in more comprehensive reviews of various subtopics on addiction in later sections of this special issue, it is anticipated that continued basic neuroscience research will aid in the development of effective therapeutic interventions for the long-term treatment of drug-dependent individuals.British Journal of Pharmacology (2008) 154, 261-274; doi:10.1038/bjp.2008 published online 3 March 2008 Keywords: abuse; addiction; animal models; dopamine; glutamate; mesocorticolimbic; neurobiology; relapse Abbreviations: AMPA, a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid; BLA, basolateral amygdala; BNST, bed nucleus of the stria terminalis; CeA, central nucleus of the amygdala; CPP, conditioned place preference;

Extended methamphetamine self-administration enhances reinstatement of drug seeking and impairs novel object recognition in rats

“…The enhanced reinstatement and the correlation between intake and drug seeking for drug-primed reinstatement is likely related to the differences in the neural circuitry that mediates reinstatement of drug seeking produced by drug-vs. cue-induced reinstatement. Studies on the neural substrates that maintain cocaine seeking have shown that the circuitries for different forms of reinstatement consist of partially overlapping yet distinctly different sets of brain nuclei (Feltenstein and See 2008). Interestingly, the opioid receptor antagonist, naltrexone, attenuated methamphetamine-primed but not conditioned-cued reinstatement (Anggadiredja et al 2004b), implicating a potential role for the opioid system in methamphetamine-primed reinstatement.…”

Comparison of the Reinforcing Properties of Nicotine and Cigarette Smoke Extract in Rats

“…Prior work has identified separate neural mechanisms underlying cue-and stress-induced reinstatement. Whereas cue-induced reinstatement is predominantly mediated by dopaminergic and glutamatergic pathways, stress-induced reinstatement involves corticotropin-releasing factor and norepinephrine (Feltenstein and See, 2008;Kalivas and McFarland, 2003). Differential effects of CSE and nicotine on these pathways may reflect their differing potencies as inhibitors of MAO-A and -B, the important regulators of catecholamine function (Bortolato et al, 2008).…”

Afferent Drive of Medial Prefrontal Cortex by Hippocampus and Amygdala is Altered in MAM-Treated Rats: Evidence for Interneuron Dysfunction

“…We demonstrated that a subpopulation of neurons of the mPFC receiving a functional input from the BLA can actively encode emotional learning (Laviolette et al, 2005). The neural networks incorporating the frontal, temporal lobes, and amygdala regulate fear memory, reward-associated learning, drug addiction, and anxiety disorders (Feltenstein and See, 2008;Fuchs et al, 2005;Maren, 2008;Orsini et al, 2011). The current study demonstrates that the BLA has an essential time-dependent facilitatory and inhibitory role in regulating vHipp-mPFC information flow, which may be significant in the gating of behavioral responses.…”