2004 - 2005 Publications > Genetics of Cocaine Addiction

Genetics of Cocaine Addiction

• Tang et al showed that CREB and iontropic glutamate receptors are increased in the VTA of cocaine overdose victims.  These results are similar to those seen in animals.  J Neurochem. 2003 May;85(4):911-24
• Makris et al showed that the absence of right-left amygdala asymmetry cocaine addicts found in normal controls is associated with cocaine dependence.  They argue that this difference is genetic.  Future studies need to validate this argument.  Neuron. 2004 Nov 18;44(4):729-40
• Szumlinski et al  have found that Homer deletions in mice mimics the behavioral and neurochemical phenotype produced by repeated cocaine administration and implicate Homer in regulating addiction to cocaine.  Homer is scaffolding protein that interacts with glutamate receptors Neuron. 2004 Aug 5;43(3):401-13
• Cocaine withdrawal induces the expression of the Activator of G protein signaling 3 (AGS3) in the prefrontal cortex that mediates cocaine induced drug seeking and sensitization Bowers et al  Neuron. 2004 Apr 22;42(2):181-3.
• Recent work by Yao et al suggest that down regulation of PSD-95, a scaffolding protein involved in clustering receptors at excitatory synapses is required for sensitization to cocaine.  This work together with the work of Kalivas and Worley points to the importance of glutamatergic projections from prefrontal cortex in regulating the action of drug of abuse. Neuron. 2004 Feb 19;41(4):625-38
• Kreibich and Blendy (UPenn) show that the cAMP response element-binding protein is required for stress but not cocaine-induced reinstatement. J.  Neurosci. 2004 Jul 28;24(30):6686-92.
• Gelernter et al identified a lod score of 4.66 for membership in the "Heavy Use, Cocaine Predominant" cluster on chromosome 12 (in EAs only) and a lod score of 3.35 for membership in the "Moderate Cocaine and Opioid Abuse" cluster on chromosome 18. Am J Med Genet B Neuropsychiatr Genet. 2005 Jul 5;136(1):45-52.
• Hemby et al demonstrated that the glutamate receptor subunits NR1, GluR1, GluR2/3 and GluR5, are upregulated in the nucleus accumbens of post-brains of cocaine addict and in monkeys that self-administered cocaine for 18 months.   These changes may underlie the glutamatergic dysfunction seen in the prefrontal cortex of cocaine addicts. J Neurochem. 2005 Dec;95(6):1785-93.
• Berrettini and colleagues identified polymorphism in intron of Homer1 that is associated with cocaine dependence in African Americans. Psychiatr Genet. 2005 Dec;15(4):277-283.
• Dahl et al  confirm the result of Kreek et al that polymorphisms in the prodynorphin promoter are associated with increased risk for becoming cocaine dependent.  Am J Med Genet B Neuropsychiatr Genet. 2005 Nov 5;139(1):106-8
• Tsai et al have discover that  mutations in the LIM-only (LMO), encoding a regulator of LIM-homeodomain proteins, that alter the locomotor response to cocaine in fruit flies. Mutations that increase expression of LMO decrease sensitivity of flies to cocaine while decreased expression of LMO increases the sensitivity of flies to cocaine.  This work suggests that there is an overlap between neuronal systems that regulate circadian rhythms and cocaine sensitivity. Future studies will determine the relevance of LMO mutations in the mouse.  PLoS Biol. 2004 Dec;2(12):e408.
• Bainton et al used a genetic screen to identify Drosophila mutants with increased sensitivity to cocaine.  Interestingly, the cocaine sensitive “moody” mutant also had increased sensitivity to nicotine, but was resistant to the acute effects of alcohol.  Molecular identification of moody revealed that it is an evolutionarily conserved G-protein coupled receptor (GPCR) of previously unknown function that is expressed in glia that also regulates the  blood barrier of flies.  Cell. 2005 Oct 7;123(1):145-56
• Kumar et al  show chromatin remodeling mediates neuronal and behavioral changes induced by cocaine.   Neuron. 2005 Oct 20;48(2):303-14.
• McClung et al found that the mouse clock gene, which mediates circadian rhythmic behaviors, also regulates cocaine reward and dopaminergic transmission.  Proc Natl Acad Sci U S A. 2005 Jun 28;102(26):9377-81
• Recent work by Miller et al  suggests that some of the actions of amphetamines and cocaine may be mediated by trace amines such as -phenylethylamine -PEA).   Recent work by the Madras laboratory has shown that cocaine prevents the uptake of -PEA) by the dopamine transporter.  J Pharmacol Exp Ther. 2005 Jun;313(3):983-94