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Table 3.

Shared genes showing significant changes in expression between control and drug treated fish

FunctionAccession numberGene name/symbolFold changePublished link to drug dependencyReference
Neurotransmission NM_131894 GRIA2 1.9 (ethanol) AMPA glutamate receptors implicated in stimulus-induced relapse 1, 2 see 3 for review 
   2.3 (nicotine)   
 XM_001340391 NMDAR1 3.9 (ethanol) Elevated NMDA R1 protein and mRNA expression associated with cocaine/ethanol dependence and withdrawal. NMDA R1 mRNA expression associated with opiate withdrawal 3–6 
   4.7 (nicotine)   
 XM_684668 Hypocretin receptor 2 0.6 (ethanol) Hypocretin receptors implicated in regulation of motivational behaviour,regulation of NMDA and AMPA receptor levels in VTA and stress induced relapse 7,8 
   0.7 (nicotine)   
Signal transduction NM_001004553 Calcineurin B 3.4 (ethanol) Role in short-term memory and reward induced CPP 
   3.6 (nicotine)   
 NM_131398 Protein phosphatase type 2C beta 1.5 (ethanol)   
   1.4 (nicotine)   
Steroid metabolism BC083388 Peripheral benzodiazepine receptor 2.8 (ethanol) Regulate steroid metabolism. Indirect regulators of GABA-A receptors. Implicated in mechanism of melatonin reversal of opiate dependence 10,11 
   3.0 (nicotine)   
 NM_199872 Oxysterol binding protein 2.0 (ethanol)   
   2.6 (nicotine)   
Cell adhesion/neural plasticity NM_131830 NCAM2 2.4 (ethanol) Roles in synaptic plasticity. Changes in cell adhesion molecule expression associated with drug dependence 12-14 
   2.3 (nicotine)   
 NM_212571 Protocadherin 10a 3.2 (ethanol)   
   3.3 (nicotine)   
 AF506734 Glial fibrillary acidic protein (GFAP) 1.5 (ethanol) Chronic morphine exposure leads to increased GFAP expression. Factors that inhibit morphine dependence and relapse prevent GFAP upregulation 15 
   1.7 (nicotine)   
Other NM_201346 Lis 1A (Lissencephaly 1) 2.6 (ethanol)   
   2.7 (nicotine)   
 BC067667 AMMECR1 (Alport syndrome, mental retardation, midface hyperplasia and elliptocytosis chromosome region 1) 2.9 (ethanol)   
   3.0 (nicotine)   
 XM_001333947 Coatomer protein subunit beta 2 0.4 (ethanol) Coatomer complex regulates D1 receptor transport 16 
   0.4 (nicotine)   
FunctionAccession numberGene name/symbolFold changePublished link to drug dependencyReference
Neurotransmission NM_131894 GRIA2 1.9 (ethanol) AMPA glutamate receptors implicated in stimulus-induced relapse 1, 2 see 3 for review 
   2.3 (nicotine)   
 XM_001340391 NMDAR1 3.9 (ethanol) Elevated NMDA R1 protein and mRNA expression associated with cocaine/ethanol dependence and withdrawal. NMDA R1 mRNA expression associated with opiate withdrawal 3–6 
   4.7 (nicotine)   
 XM_684668 Hypocretin receptor 2 0.6 (ethanol) Hypocretin receptors implicated in regulation of motivational behaviour,regulation of NMDA and AMPA receptor levels in VTA and stress induced relapse 7,8 
   0.7 (nicotine)   
Signal transduction NM_001004553 Calcineurin B 3.4 (ethanol) Role in short-term memory and reward induced CPP 
   3.6 (nicotine)   
 NM_131398 Protein phosphatase type 2C beta 1.5 (ethanol)   
   1.4 (nicotine)   
Steroid metabolism BC083388 Peripheral benzodiazepine receptor 2.8 (ethanol) Regulate steroid metabolism. Indirect regulators of GABA-A receptors. Implicated in mechanism of melatonin reversal of opiate dependence 10,11 
   3.0 (nicotine)   
 NM_199872 Oxysterol binding protein 2.0 (ethanol)   
   2.6 (nicotine)   
Cell adhesion/neural plasticity NM_131830 NCAM2 2.4 (ethanol) Roles in synaptic plasticity. Changes in cell adhesion molecule expression associated with drug dependence 12-14 
   2.3 (nicotine)   
 NM_212571 Protocadherin 10a 3.2 (ethanol)   
   3.3 (nicotine)   
 AF506734 Glial fibrillary acidic protein (GFAP) 1.5 (ethanol) Chronic morphine exposure leads to increased GFAP expression. Factors that inhibit morphine dependence and relapse prevent GFAP upregulation 15 
   1.7 (nicotine)   
Other NM_201346 Lis 1A (Lissencephaly 1) 2.6 (ethanol)   
   2.7 (nicotine)   
 BC067667 AMMECR1 (Alport syndrome, mental retardation, midface hyperplasia and elliptocytosis chromosome region 1) 2.9 (ethanol)   
   3.0 (nicotine)   
 XM_001333947 Coatomer protein subunit beta 2 0.4 (ethanol) Coatomer complex regulates D1 receptor transport 16 
   0.4 (nicotine)   

Selected examples of genes that showed a significant change in expression in brain tissue from fish treated with either nicotine (30 μmol l–1, 20 min day–1) or ethanol (175 mmol l–1, 20 min day–1) following 3 weeks of withdrawal. Only genes that showed similar changes in expression in both sample groups are included. Potential link to dependency, where known, are given. Changes in expression of genes highlighted in bold were validated by Q-RT-PCR (Fig. 5B)

References: (1) (Mead and Stephens,2003), (2) (Sanchis-Segura et al., 2006), (3) (Kalivas,2004), (4) (Follesa and Ticku,1995), (5) (Noda and Nabeshima, 2004), (6) (Ahmed et al., 2005), (7) (Boutrel,2005), (8) (Borgland et al.,2006), (9) (Biala et al.,2005), (10) (Sanna et al.,2004), (11) (Raghavendra and Kulkarni, 1999), (12) (Weber et al., 2006), (13) (Miller et al., 2006), (14) (Abrous et al., 2002), (15) (Alonso et al., 2007), (16) (Bermak et al., 2002)

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