Overexpression of 5-HT1B mRNA in nucleus accumbens shell projection neurons differentially affects microarchitecture of initiation and maintenance of ethanol consumption

Serotonin 1B (5-HT1B) heteroreceptors on nucleus accumbens shell (NAcSh) projection neurons have been shown to enhance the voluntary consumption of alcohol by rats, presumably by modulating the activity of the mesolimbic reward pathway. The present study examined whether increasing 5-HT1B receptors expressed on NAcSh projection neurons by means of virus-mediated gene transfer enhances ethanol consumption during the initiation or maintenance phase of drinking and alters the temporal pattern of drinking behavior. Animals received stereotaxic injections of viral vectors expressing either 5-HT1B receptor and green fluorescent protein (GFP) or GFP alone. Home cages equipped with a three-bottle (water and 6 and 12% ethanol) lickometer system recorded animals’ drinking behaviors continuously, capturing either initiation or maintenance of drinking behavior patterns. Overexpression of 5-HT1B receptors during initiation increased consumption of 12% ethanol during both forced-access and free-choice consumption. There was a shift in drinking pattern for 6% ethanol with an increase in number of drinking bouts per day, although the total number of drinking bouts for 12% ethanol was not different. Finally, increased 5-HT1B expression induced more bouts with very high–frequency licking from the ethanol bottle sippers. During the maintenance phase of drinking, there were no differences between groups in total volume of ethanol consumed; however, there was a shift toward drinking bouts of longer duration, especially for 12% ethanol. This suggests that during maintenance drinking, increased 5-HT1B receptors facilitate longer drinking bouts of more modest volumes. Taken together, these results indicate that 5-HT1B receptors expressed on NAcSh projection neurons facilitate ethanol drinking, with different effects during initiation and maintenance of ethanol-drinking behavior.