Increased expression of 5-HT1B receptors in rat nucleus accumbens via virally mediated gene transfer increases voluntary alcohol consumption.
Serotonin 5-HT(1B) receptors have been linked to alcoholism in humans and alcohol consumption in rodents. We hypothesize that these receptors, which are located on the axon terminals of nucleus accumbens' (NAcc) projection neurons, modulate alcohol reward mechanisms. To test this hypothesis, we measured ethanol consumption by rats that received bilateral microinjections of a viral vector producing 5-HT(1B) overexpression (HA1B/GFP). Other groups received either control (GFP-only) herpes simplex viral vectors into the medial NAcc shell or were handled briefly with no surgery. All animals were housed singly and had continuous access to water, 6% ethanol, and 12% ethanol in their home cages both before and after surgery. There were no differences in the amount or rate of weight gain, amount of food eaten, or total fluid consumed. There were also no differences in the amount of ethanol consumed between groups prior to surgery. However, after surgery, the HA1B/GFP group consumed twice as much ethanol as the other groups. The main effect of total ethanol consumption was significant (p<.05); the control groups did not differ from each other. Whereas there were no between-group differences in 6% ethanol consumption, there was a large increase in the amount of 12% ethanol consumed by the HA1B/GFP-expressing animals compared to the two control groups as well as to their own presurgery intake (p<.05). We hypothesize that increased 5-HT(1B) expression in NAcc led to either greater reward or reduced aversive effects from the 12% ethanol, thereby leading to increased voluntary ethanol consumption.
Hoplight
B J
BJ
Department of Psychiatry and Behavioral Sciences, University of Washington Medical School, Box 359911, Harborview Medical Center, 325 - 9th Avenue, Seattle, WA 98104, USA.
Sandygren
N A
NA
Neumaier
J F
JF
D000428:Alcohol Drinking / Q000503:physiopathology*; D000818:Animals; D004435:Eating; D000431:Ethanol / Q000008:administration & dosage; D015870:Gene Expression; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000235:genetics; D006388:Hemagglutinins; D008297:Male; D009714:Nucleus Accumbens / Q000378:metabolism*; D051381:Rats; D020318:Rats, Long-Evans; D044302:Receptor, Serotonin, 5-HT1B / Q000235:genetics* / Q000502:physiology; D011993:Recombinant Fusion Proteins; D018139:Simplexvirus / Q000235:genetics; D014162:Transfection; D015430:Weight Gain
D006388:Hemagglutinins; D044302:Receptor, Serotonin, 5-HT1B; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D000431:Ethanol