Increased alcohol self-administration following exposure to the predator odor TMT in active coping female rats - PubMed (original) (raw)

Increased alcohol self-administration following exposure to the predator odor TMT in active coping female rats

Laura C Ornelas et al. Behav Brain Res. 2021.

Abstract

Post-traumatic stress disorder (PTSD) and alcohol use disorder (AUD) are highly comorbid. Additionally, individual differences in response to stress suggest resilient and susceptible populations. The current study exposed male and female Long Evans rats to the synthetically produced predator odor 2,5-dihydro-2,4,5-trimethylthiazoline (TMT) to examine individual differences in stress-reactive behaviors (digging and immobility) and whether these differences were related to subsequent alcohol drinking. Male and female Long Evans rats were trained on operant alcohol self-administration. After 9 sessions, rats underwent exposure to TMT or water (Control) in a distinct context. 6 days after TMT exposure, rats underwent re-exposure to the TMT-paired context (without TMT), and a series of behavioral assessments (acoustic startle, zero maze, light/dark box), after which rats resumed alcohol self-administration. TMT subgroups were created using a ratio of digging to immobility behavior during TMT exposure and rats with a ratio score < 1.0 or> 1.0 were grouped into TMT-1 (low digging/high immobility) or TMT-2 (high digging/low immobility), respectively. All male rats exposed to TMT met criteria for TMT-1, while female rats were divided into the two subgroups. In females, high digging/low immobility behavior during TMT exposure (TMT-2) was related to increased alcohol self-administration, but this was not observed in males or females that engaged in low digging/high immobility (TMT-1). These data show that individual differences in stress-reactivity can lead to lasting behavioral changes which may lead to a better understanding of increases in alcohol drinking following stress in females.

Keywords: Alcohol; Alcohol use disorder; Individual differences; Post-traumatic stress disorder; Predator odor stress; Sex differences; TMT.

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Conflict of interest statement

Conflict of interest

None.

Figures

Figure 1.. Experimental Timeline.

Male and female Long-Evans rats were trained on alcohol self-administration for 9 days. 24 hr post last self-administration training day, male and female rats were exposed to water or TMT. 6 days later, rats were re-exposed to the initial TMT-paired contextual environment in the absence of TMT. 24 hr later rats underwent testing for anxiety-like behavior (zero maze, hyperarousal (acoustic startle response, ASR) and anxiety-like behavior as measured by approach/avoidance behavior (light/dark test and zero maze). Three days after behavioral tests, rats returned to alcohol self-administration for 30 sessions (15A). The sample size of each treatment group for male and female rats is also included.

Figure 2.. Distribution plots to illustrate range of stress-reactive behaviors between male and female rats exposed to TMT.

(A) Male and female rats exposed to TMT showed no difference in total defensive digging. (B) Male rats exposed to TMT spend significantly more total time immobile compared to female rats exposed to TMT. (C) Representation of digging/immobility scores in male and female TMT-groups 1 and 2. No male rats met the criteria for TMT-2., *p < 0.05. Mean ± SEM.

Figure 3.. Effects of TMT exposure on stress-reactive behaviors, context reactivity, and alcohol self-administration in male rats

. All male rats exposed to TMT were grouped into TMT-1. Male rats in TMT-1 performed significantly more defensive digging compared to controls (A), as well as across 10 min of the TMT exposure (B). Male rats in TMT-1 exhibited significantly more time immobile (C), as well as across time (D). Male rats in TMT-1 exhibited higher plasma corticosterone compared to controls (E). During context re-exposure, males in TMT-1 performed significant more digging (F), as well as across time (G) compared to controls. Males previously exposed to TMT showed no changes in total time immobile (H) or across time (I), as well as no changes in plasma corticosterone (J) compared to controls. Lastly, males in TMT-1 exhibited no significant increases in alcohol lever responses (K) or alcohol intake (g/kg) (L). For panels K and L, BL (baseline average) is represented to the left of the axis break. *p < 0.05. Mean ± SEM. * by group labels = main effect of group, X-axes * = main effect of time or session.

Figure 4.. Effects of TMT exposure on stress-reactive behaviors, context reactivity, and alcohol self-administration in female rats.

Female rats in TMT-2 performed significantly more defensive digging compared to controls and TMT-1 (A), as well as across the 10 min TMT exposure (B). Female rats in TMT-1 exhibited significantly more time immobile compared to controls and TMT-2 (C), as well as across 10 min of the TMT exposure (D). Female rats in TMT-2 exhibited higher plasma corticosterone levels compared to controls (E). During context re-exposure, female rats in TMT-2 performed greater total time digging (F), as well as across time (G) compared to controls. There were no changes in total time immobile in TMT-2 (H); however, across time, TMT-2 performed significantly lower immobility behavior compared to controls (I). Female rats in TMT-1 exhibited greater plasma corticosterone levels compared to controls and TMT-2. Female rats in TMT-2 performed significantly greater alcohol lever responses compared to controls (K) and alcohol intake (g/kg) (L) compared to controls. For panels K and L, BL (baseline average) is represented to the left of the axis break. * p < 0.05 vs. controls, # p < 0.05 vs. TMT-2, + p < 0.05 vs. TMT-1. Mean ± SEM. Dotted line denotes moving to MWF sessions. * by group labels = main effect of group, X-axes * = main effect of time or session.

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Increased alcohol self-administration following exposure to the predator odor TMT in active coping female rats - PubMed (original) (raw)