Sex Differences in Affective States and Association with Voluntary Ethanol Intake in Sprague Dawley Rats

Abstract

Alcohol use disorders (AUDs) are a major problem across the United States. While AUD remains a complex human condition, it is difficult to isolate the directionality of anxiety and ethanol (EtOH) drinking from outside influences. The present study sought to investigate the relationship between affective states and EtOH intake using male and female Sprague Dawley rats. Using complementary tests of anxiety- and depressive-like behavior, we found sex- and test-specific differences in basal affective behavior such that females displayed enhanced anxiety-like behavior in the Splash Test and males displayed enhanced anxiety-like behavior in the Novelty Suppressed Feeding Test. Although there were no sex differences in EtOH intake and no correlation between anxiety-like behavior and subsequent EtOH intake, we did find that depressive-like behavior predicted future EtOH intake in females rats only. In addition, we observed an increase in depressive-like behavior is male rats in both the water and EtOH drinking groups. Furthermore, anxiety-like behavior, but not depressive-like behavior predicted subsequent EtOH intake in female rats. Lastly, we found a history of EtOH intake decreased pain thresholds in male and female rats. Together, these experiments provide important information on the complex interaction between negative affect and alcohol intake and how these two contexts reciprocally do, or do not, influence each other in a sex-specific manner.

Sex‐related differences in pattern of ethanol drinking under the intermittent‐access model and its impact on exploratory and anxiety‐like behavior in Long‐Evans rats

“…While it cannot be ruled out that this delay in stabilization in female drinking could be attributable to estrous cycle fluctuations, we believe this is unlikely, in light of prior findings that intermittent‐access EtOH drinking is not dependent on estrous cycle stage (Li et al, 2019; Priddy et al, 2017) and that our subjects were run in three separate cohorts. While a number of other studies that examined intermittent‐access EtOH‐drinking in rats have similarly found higher levels of drinking and preference in females compared to males (Li et al, 2019; Loi et al, 2014; McNamara & Ito, 2021; Priddy et al, 2017), others have reported no difference (Quadir et al, 2022; Schramm‐Sapyta et al, 2014). Of the two published studies that specifically examined Long‐Evans rats drinking 20% EtOH, one reported that females drank more than males over 5 weeks of access (McNamara & Ito, 2021), while the other found that females drank more over the first 3 weeks of access, but not during subsequent weeks (Morales et al, 2015).…”

“…Examining weekly levels of intermittent access 20% EtOH drinking, different studies have reported different patterns. While some have found escalating levels of intake across weeks in both males and females (Loi et al, 2014; Schramm‐Sapyta et al, 2014), others have found it in males but not females (Morales et al, 2015) or in neither males nor females (Quadir et al, 2022). In our own work with males, we have previously observed both stable intake across all access weeks and escalation until week 3 or 4 of access (Barson et al, 2015; Pandey et al, 2019), so part of this measure may depend on other experimental conditions.…”

“…To our knowledge, this is the first time that the 24‐h intake of male or female rats has been described for this access model. Prior research has found that rats drink a high percentage of their daily intake in the first 30 min of access (Barson et al, 2015; Quadir et al, 2022) and that most consumption occurs during the dark cycle (Bell et al, 2011). Similarly, across a 24‐h period in a 15‐day on, 15‐day off intermittent‐access model, male and female P and HAD2 rats were found to follow a circadian pattern of EtOH intake, although this was not statistically compared between the sexes (Rosenwasser et al, 2014).…”

“…Under two‐bottle‐choice ad libitum access paradigms, females have been found to drink more EtOH than males over a range of EtOH concentrations and rodent strains, including Long‐Evans rats, Wistar rats, selectively bred alcohol‐preferring AA and P rats, and WSC‐1 mice (Bell et al, 2011; Eriksson, 1972; Priddy et al, 2017; Tambour et al, 2008). A few, but not all, studies have also found that females show elevated EtOH intake and preference under intermittent access 16% to 20% EtOH two‐bottle‐choice paradigms (Li et al, 2019; Loi et al, 2014; McNamara & Ito, 2021; Morales et al, 2015; Priddy et al, 2017; Quadir et al, 2022; Schramm‐Sapyta et al, 2014), with no effects of estrous cycle stage (Li et al, 2019; Priddy et al, 2017). To our knowledge, no studies have examined patterns of EtOH drinking under the intermittent‐access model across the 24 h of daily access to determine if there are qualitative sex‐related differences in EtOH drinking.…”

Chronic Alcohol Drinking Drives Sex-Specific Differences in Affective Behavior and Medial Prefrontal Cortex Activity in CRF1:Cre:Tdtomato Transgenic Rats

“…Intermittent access two bottle choice alcohol drinking was performed as previously described (Quadir et al, 2022; Quadir et al, 2020b; Quadir et al, 2021b; Wise, 1973). After 4d acclimatization to water bottle drinking, one bottle containing 20% EtOH and one bottle of water for 24h were placed on cages on alternating days.…”