URF26-PSY-HahR - Results & Conclusions

Figure 1: Number of rewards per session. Two-way repeated measures ANOVA suggests significance between sessions (F6,154=16.80, p<0.0001). There was no interaction between sex and session.

Figure 3: Number of correct responses per session. Two-way repeated measures ANOVA suggest significance between sessions (F6, 132=23.74, p<0.0001. There was no interaction between sex and session.

Figure 2: Volume consumption (mg/kg) of 10% EtOH per session. Two-way repeated measures ANOVA suggests significance between sessions (F4.429,97.45=6.043, p=0.0001), and an interaction between session and sex, (F4.429, 97.45=4.343, p=0.0020). Šidák multiple comparisons test suggests a significant difference between males and females on session 5, (p=0.0065).

Figure 4: Sip count by session. Two-way repeated measures ANOVA suggests significance between sessions (F6,132= 4.689, p=0.0002). There was no interaction between sex and session.

Conclusions:

● Prior to foot shock, subjects between both sexes showed decreased levels in correct responding and earned rewards across sessions; however, there was in increase in volume consumption and sip count.

● This pattern could imply a compensatory increase in intake per access period. Reduced opportunities led to an intensified consumption, which reflects motivation was preserved for EtOH despite reduced responses.

● Furthermore, for volume consumption, there was an interaction between sex and session. This indicates that volume consumption between sexes was not the same for every session, or in other words, the relationship varied. Males and females were also significantly different on session 5.

● Foot shock showed decreased levels for all parameters, with the higher output reducing levels the most.

● Additionally, for volume consumption, males showed a statistically significant decrease in consumption when comparing sessions 6 and 7 to session 5 (p=0.0036 and 0.0016), while females only reduced their consumption on session 7 (p=0.0366). These findings suggest that females are more resistant to foot shock than males, which is consistent with prior literature5. However, this did not occur in correct responses, which was not anticipated.

● Overall, we found that foot shock is an efficient mechanism to decrease ethanol self-administration in male and female mice.

Future Directions

Building on this control experiment, we are testing whether a viral injection of DREADD/DIO virus into the nucleus accumbens (NAc) shell that is selectively designed to inhibit neuronal activity will alter reward and drug seeking behavior in Chat-Cre+ mice.
In the first experiment, animals will have access to sucrose via the lickometer in the operant chambers, while in the second experiments animals will have access to fentanyl.
Animals in both the experiments will be habituated and on the testing day, these animals will receive an i.p. CNO injection that is designed to activate the DREADD/DIO virus as opposed to an i.p. saline injection on the baseline day.
We hypothesize that animals will exhibit less reward and drug seeking behaviors on the testing day when injected with CNO as compared to the saline injection.