Medial Prefrontal Cortical Dopamine Responses During Operant Self-Administration of Sweetened Ethanol

Abstract

Background: Medial prefrontal cortex (mPFC) dysfunction is present in heavy alcohol consumers. Dopamine signaling in mPFC is associated with executive functioning and affects drinking behavior; however, direct measurement of extracellular mPFC dopamine during appetitive and consummatory ethanol (EtOH) self-administration behavior has not been reported.

Methods: We used in vivo microdialysis in freely behaving, adult, male, Long Evans rats to determine extracellular dopamine concentration in the mPFC during operant self-administration of an EtOH-plus-sucrose or sucrose solution. The model separated appetitive/seeking from consummatory phases of the operant session. Dopamine was also monitored in an untrained handling control group, and dialysate EtOH was measured in the EtOH-drinking group.

Results: Home cage baseline dopamine was lower in rats that experienced a week of drinking sweetened EtOH compared with sucrose-drinking and handling controls. Transfer into the operant chamber and the initiation of consumption stimulated a relatively higher change in dopamine over baseline in the sweetened EtOH group compared with sucrose and handling controls. However, all groups show a dopamine response during transfer into the operant chamber, and the sucrose group had a relatively higher change in dopamine over baseline during initiation of consumption compared with handling controls. The time courses of dopamine and EtOH in the mPFC differ in the EtOH-consuming rats.

Conclusions: Differences in extracellular mPFC dopamine between EtOH drinkers compared with control groups suggest that mPFC dopamine is involved in the mechanism of operant self-administration of sweetened EtOH and sucrose. Furthermore, the increase in dopamine during consumption is consistent with a role of mPFC dopamine in reward prediction.

Keywords: Appetitive; Consumption; Ethanol; Ethanol-Seeking; Mesocortical; Operant Self-Administration.

Fig. 1

Time course of the operant self-administration session. On the eighth day of operant testing, consecutive 7-minute dialysis samples were taken during all behavioral phases except for the final wait period sample which was variable due to the bar-press period. Figure adapted from Schier and colleagues (2013).

Fig. 2

Dialysate dopamine concentrations in medial prefrontal cortex (mPFC) during home cage baseline, wait, drink and postdrink periods for the sucrose and handling controls along with rats trained to drink 10S10E. For clarity, only group comparisons are shown on the figure as follows. *Significant difference between the 10S10E group compared with either the 10S or handling groups during the baseline and wait periods. #Drink and postdrink period dopamine concentrations were significantly different in 10S compared with either the 10S10E or handling groups. Not indicated in the figure are significant increases in dopamine at the first sample during the wait period compared with the remaining samples. Similarly, there was a significant increase in dopamine during the first drink sample compared with the remaining drink and postdrink samples. Overall significant main effects of time and a group-by-time interaction occurred. Data represented as mean ±SEM for most points, but selected error bars are omitted for clarity (n =9 for each group). 10S10E = 10% sucrose + 10% ethanol, 10S = 10% sucrose.

Fig. 3

Licks in 7-minute bins. *Significant difference in licks between 10S10E (n =9; 10% sucrose + 10% ethanol) and 10S (n =9; 10% sucrose) groups. Data represented as mean ±SEM. 10S10E = 10% sucrose + 10% ethanol, 10S = 10% sucrose.

Fig. 4

Medial prefrontal cortex dopamine relative to home cage baseline during home cage baseline, wait, drink and postdrink periods. The data shown in Fig. 2 were transformed to percent of home cage baseline. For clarity, only group comparisons are shown on the figure as follows. *Significant difference between the 10S10E group compared with either the 10S or handling groups during the wait period. #Drink and postdrink period dopamine responses above baseline were significantly different in each group compared with the other 2 groups. Overall, significant main effects of time, group, and a group-by-time interaction occurred. Data represented as mean ±SEM for most points, but selected error bars are omitted for clarity (n =9 for each group). 10S10E = 10% sucrose + 10% ethanol, 10S = 10% sucrose.

Fig. 5

Dopamine and ethanol (EtOH) concentrations in medial prefrontal cortex (mPFC) during the drink and postdrink periods in the 10S10E group. Left y-axis shows the dialysate EtOH concentrations (circles). Right y-axis shows the percent change in mPFC dopamine concentration during the drink and postdrink periods relative to home cage baseline (squares, same data shown in Fig. 3). The bottle retracted from the chamber after the third sample. Data represented as mean ±SEM (n =9). 10S10E = 10% sucrose + 10% ethanol.

Fig. 6

Microdialysis probe placements within the medial prefrontal cortex. Coronal slices 2.7, 3.2, and 3.7 mm from bregma showing microdialysis probe placements for all experimental groups. Lines represent 3.25 mm active dialysis area. 10S10E = 10% sucrose + 10% ethanol, 10S = 10% sucrose. Histology figure adapted from Paxinos and colleagues (1998).