9 Neurobiology of addiction

Trevor is Professor of Cognitive Neuroscience, being elected to the Chair of Expt. Psychology (and Head of Department) at the University of Cambridge, from October 2002. He is a Fellow of the British Psychological Society (1990), the Academy of Medical Sciences (2000), and the Royal Society (2005). He received the Distinguished Scientific Contribution Award for 2011 from the American Psychological Association. He has published about 750 full papers, with an H index of about 167. He has co-edited eight books, most recently Translational Neuropsychopharmacology (Springer, 2016). Trevor directs the University of Cambridge ‘Behavioural and Clinical Neuroscience Institute’, the mission of which is to enhance translation from basic to clinical neuroscience. His interest in translation began with his co-invention of the CANTAB computerised neuropsychological battery, which is currently used in over 700 institutes and clinical centres world-wide. He stepped down as President of the British Neuroscience Association in 2011 and was made a CBE in the New Year’s Honours list of the U.K. in 2012. In 2014, he shared the ‘Brain Prize’ of the Grete Lundbeck European Brain Research Foundation, the most valuable in neuroscience, and in 2015 he received the “Lifetime Achievement Award” of the British Association for Psychopharmacology’. Much evidence, based on experimental studies of intravenous drug self-administration in experimental animals and neuroimaging studies in humans now supports the view that drug addiction results in part from aberrant learning mediated by dopamine-dependent processes of the limbic-striatal interface, including the amygdala and nucleus accumbens. The neural systems of this interface and other frontostriatal networks mediate several relevant forms of learning, including Pavlovian conditioning, goal-directed, action-outcome learning, and stimulus-response habit learning (which is not controlled by outcomes or goals). Hypothetically, drug addiction involves an imbalance between instrumental behaviour controlled by outcomes and habitual responding mediated by stimulus-response associations, corresponding hypothetically to a devolution of neurobehavioural control from (i) the prefrontal cortex to the striatum, and (ii) from the ventral to the dorsal striatum (Everitt and Robbins 2016). I will consider the experimental evidence relevant to these predictions from studies of both experimental animals and humans with substance use disorders. I will focus especially on stimulant drugs, but will consider other substance use disorders, as well the latter as part of a ‘impulse-compulsive’ spectrum of mental health disorders. For human drug abuse, it is difficult to unravel predispositions or causal neurobehavioural factors contributing to addiction, from potential neurotoxic effects of the drugs themselves. I will thus describe strategies for determining the aetiological role of these factors, based on evidence from (i) experimental animals, using several techniques and (ii) human drug abusers or vulnerable adolescents, based on functional neuroimaging methods, employing both longitudinal and endophenotype designs. I will conclude that both types of influence contribute to the drive to addiction. Finally, I will consider implications of this evidence for possible new therapeutic approaches to drug addiction, whether pharmacological or behavioural. Reference . Everitt BJ, Robbins TW. Drug addiction: updating actions to habits to compulsions ten years on. annual review of psychology2016;67:23–50.