Perspectives on current directions in the neurobiology of addiction disorders relevant to genetic risk factors.
ABSTRACT There is a significant heritability of drug addiction disorders, but potential genes that may underlie such vulnerability have not been clearly identified. Common neurobiological candidates for drug abuse include genes related to dopamine, opioid neuropeptide, and glutamate transmission that play important roles in drug reward and inhibitory control. This article provides an overview of genetic polymorphisms linked to these neurobiological systems, particularly in relation to psychostimulant- and opioid-addiction vulnerability.
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ABSTRACT: After Golgi-Cajal mapped neural circuits, the discovery and mapping of the central monoamine neurons opened up for a new understanding of interneuronal communication by indicating that another form of communication exists. For instance, it was found that dopamine may be released as a prolactin inhibitory factor from the median eminence, indicating an alternative mode of dopamine communication in the brain. Subsequently, the analysis of the locus coeruleus noradrenaline neurons demonstrated a novel type of lower brainstem neuron that monosynaptically and globally innervated the entire CNS. Furthermore, the ascending raphe serotonin neuron systems were found to globally innervate the forebrain with few synapses, and where deficits in serotonergic function appeared to play a major role in depression. We propose that serotonin reuptake inhibitors may produce antidepressant effects through increasing serotonergic neurotrophism in serotonin nerve cells and their targets by transactivation of receptor tyrosine kinases (RTK), involving direct or indirect receptor/RTK interactions. Early chemical neuroanatomical work on the monoamine neurons, involving primitive nervous systems and analysis of peptide neurons, indicated the existence of alternative modes of communication apart from synaptic transmission. In 1986, Agnati and Fuxe introduced the theory of two main types of intercellular communication in the brain: wiring and volume transmission (WT and VT). Synchronization of phasic activity in the monoamine cell clusters through electrotonic coupling and synaptic transmission (WT) enables optimal VT of monoamines in the target regions. Experimental work suggests an integration of WT and VT signals via receptor-receptor interactions, and a new theory of receptor-connexin interactions in electrical and mixed synapses is introduced. Consequently, a new model of brain function must be built, in which communication includes both WT and VT and receptor-receptor interactions in the integration of signals. This will lead to the unified execution of information handling and trophism for optimal brain function and survival.Brain Research Reviews 09/2007; 55(1):17-54. DOI:10.1016/j.brainresrev.2007.02.009 · 5.93 Impact Factor
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ABSTRACT: Individual differences in traits such as impulsivity involve high reward sensitivity and are associated with risk for substance use disorders. The ventral striatum (VS) has been widely implicated in reward processing, and individual differences in its function are linked to these disorders. Dopamine (DA) plays a critical role in reward processing and is a potent neuromodulator of VS reactivity. Moreover, altered DA signaling has been associated with normal and pathological reward-related behaviors. Functional polymorphisms in DA-related genes represent an important source of variability in DA function that may subsequently impact VS reactivity and associated reward-related behaviors. Using an imaging genetics approach, we examined the modulatory effects of common, putatively functional DA-related polymorphisms on reward-related VS reactivity associated with self-reported impulsivity. Genetic variants associated with relatively increased striatal DA release (DRD2 -141C deletion) and availability (DAT1 9-repeat), as well as diminished inhibitory postsynaptic DA effects (DRD2 -141C deletion and DRD4 7-repeat), predicted 9-12% of the interindividual variability in reward-related VS reactivity. In contrast, genetic variation directly affecting DA signaling only in the prefrontal cortex (COMT Val158Met) was not associated with variability in VS reactivity. Our results highlight an important role for genetic polymorphisms affecting striatal DA neurotransmission in mediating interindividual differences in reward-related VS reactivity. They further suggest that altered VS reactivity may represent a key neurobiological pathway through which these polymorphisms contribute to variability in behavioral impulsivity and related risk for substance use disorders.Molecular Psychiatry 10/2007; 14(1):60-70. DOI:10.1038/sj.mp.4002086 · 15.15 Impact Factor
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ABSTRACT: Pain and substance abuse co-occur frequently, and each can make the other more difficult to treat. A knowledge of pain and its interrelationships with addiction enhances the addiction specialist's efficacy with many patients, both in the substance abuse setting and in collaboration with pain specialists. This article discusses the neurobiology and clinical presentation of pain and its synergies with substance use disorders, presents methodical approaches to the evaluation and treatment of pain that co-occurs with substance use disorders, and provides practical guidelines for the use of opioids to treat pain in individuals with histories of addiction. The authors consider that every pain complaint deserves careful investigation and every patient in pain has a right to effective treatment.Addiction science & clinical practice 07/2008; 4(2):4-25. DOI:10.1151/ascp08424