Identification of neurotransmitter receptor genes involved in alcohol self-administration in the rat prefrontal cortex, hippocampus and amygdala.
About half of the risk to develop alcoholism is related to genetic background and it is well known that alcohol consumption is highly individualized. In this study, we investigated how individual alcohol consumption behaviour in Wistar rats correlated with mRNA expression of 20 genes in the prefrontal cortex, hippocampus and amygdala. We found that the long-term alcohol consumption of an individual could be estimated by the mean of its consumption on Day 2 and 3. This short exposure minimized changes in gene expression induced by alcohol itself. We found a positive correlation in the prefrontal cortex of GABA(A) alpha5 (r=0.96), GABA(B1) (r=0.96), AMPA GluR1 (r=0.93), 5-HT(3A) (r=0.93) and the alpha adrenoceptors (alpha(1A)r=1.00, alpha(1B)r=0.93, alpha(2A)r=0.93) with consumption. In the hippocampus, we found negative correlations with the NMDA NR2A subunit (r=-0.86), the alpha(1A) adrenoceptor (r=-0.89) and the glucocorticoid receptor (r=-0.86). Finally, in the amygdala there was a negative correlation to NMDA NR2A (r= -0.79) and a positive correlation with serotonin 5-HT(2C) (r=0.79). In conclusion, we have used qPCR to identify specific genes in the brain that correlated to alcohol self-administration of an individual animal. This study suggests that alcohol consumption in the early stages of acquisition depends on the genetic background of the individual and that the prefrontal cortex is particularly important in this behaviour.
Pickering
Chris
C
Karolinska Institutet, Department of Clinical Neuroscience, Division of Drug Dependence Research, SE-17176, Stockholm, Sweden. Chris.Pickering@ki.se
Avesson
Lotta
L
Lindblom
Jonas
J
Liljequist
Sture
S
Schiöth
Helgi B
HB
D000428:Alcohol Drinking / Q000235:genetics*; D000679:Amygdala / Q000378:metabolism*; D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D017931:DNA Primers; D018076:DNA, Complementary / Q000096:biosynthesis; D004327:Drinking Behavior / Q000187:drug effects; D015870:Gene Expression / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D017397:Prefrontal Cortex / Q000378:metabolism*; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D051381:Rats; D017208:Rats, Wistar; D017981:Receptors, Neurotransmitter / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012439:Saccharin / Q000494:pharmacology
D017931:DNA Primers; D018076:DNA, Complementary; D017981:Receptors, Neurotransmitter; D012313:RNA; D012439:Saccharin