Withdrawal from Brief Repeated Alcohol Treatment in Adolescent and Adult Male and Female Rats

Fleming, W.A.J.; Jones, Quincy; Chandra, Upasana; Saini, Aashna; Walker, David W.; Francis, Reynold; Ocampo, Gabriela; Kuhn, Cynthia M.

doi:10.1111/acer.13936

Cited by 10 publications

(10 citation statements)

References 55 publications

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“…The majority of the studies performed either with rats (117)(118)(119)(120)(121)(122)(123) or mice (63, [124][125][126][127][128][129][130] have failed to show sex-differences in this test. In some of these studies direct comparisons among strains (97,131,132) and/or age of the animals (133,134), which are critically-relevant variables, were performed but no sex-related effect was found. There are however, a few reports showing that females are more (135)(136)(137)(138) or less (139)(140)(141)(142)(143) anxious than males.…”

Section: Light-dark Transition Testmentioning

confidence: 99%

Effect of Estrous Cycle on Behavior of Females in Rodent Tests of Anxiety

2021

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Anxiety disorders are more prevalent in women than in men. In women the menstrual cycle introduces another variable; indeed, some conditions e.g., premenstrual syndrome, are menstrual cycle specific. Animal models of fear and anxiety, which form the basis for research into drug treatments, have been developed almost exclusively, using males. There remains a paucity of work using females and the available literature presents a confusing picture. One confound is the estrous cycle in females, which some authors consider, but many do not. Importantly, there are no accepted standardized criteria for defining cycle phase, which is important given the rapidly changing hormonal profile during the 4-day cycle of rodents. Moreover, since many behavioral tests that involve a learning component or that consider extinction of a previously acquired association require several days to complete; the outcome may depend on the phase of the cycle on the days of training as well as on test days. In this article we consider responsiveness of females compared to males in a number of commonly used behavioral tests of anxiety and fear that were developed in male rodents. We conclude that females perform in a qualitatively similar manner to males in most tests although there may be sex and strain differences in sensitivity. Tests based on unconditioned threatening stimuli are significantly influenced by estrous cycle phase with animals displaying increased responsiveness in the late diestrus phase of the cycle (similar to the premenstrual phase in women). Tests that utilize conditioned fear paradigms, which involve a learning component appear to be less impacted by the estrous cycle although sex and cycle-related differences in responding can still be detected. Ethologically-relevant tests appear to have more translational value in females. However, even when sex differences in behavior are not detected, the same outward behavioral response may be mediated by different brain mechanisms. In order to progress basic research in the field of female psychiatry and psychopharmacology, there is a pressing need to validate and standardize experimental protocols for using female animal models of anxiety-related states.

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Section: Light-dark Transition Testmentioning

confidence: 99%

Effect of Estrous Cycle on Behavior of Females in Rodent Tests of Anxiety

2021

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“…Chronic exposure to alcohol and other drugs of abuse causes long-term changes in reward processing that are thought to promote a continued escalation of substance use. Even though positive hedonic feelings occur shortly after the drug intake, negative hedonic responses follow-especially after repeated exposures-due to alterations in the brain reward system and stress-related structures such as the extended amygdala, resulting in a withdrawal syndrome including dysphoria, irritability, anxiety, and other negative emotional states (Zhang and Schulteis, 2008;Leventhal et al, 2013;Su et al, 2017;Fleming et al, 2019). Some hypothesize that over time the desire to avoid the negative feelings associated with withdrawal becomes the primary motivational factor for compulsive drug-seeking behavior (Solomon and Corbit, 1974;Koob and Volkow, 2010).…”

Section: Overlapping Effects Of Trauma and Drugs On Neuronal And Endomentioning

confidence: 99%

Mechanisms of Shared Vulnerability to Post-traumatic Stress Disorder and Substance Use Disorders

Maria-Rios

Morrow

2020

Front. Behav. Neurosci.

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Psychoactive substance use is a nearly universal human behavior, but a significant minority of people who use addictive substances will go on to develop an addictive disorder. Similarly, though ∼90% of people experience traumatic events in their lifetime, only ∼10% ever develop post-traumatic stress disorder (PTSD). Substance use disorders (SUD) and PTSD are highly comorbid, occurring in the same individual far more often than would be predicted by chance given the respective prevalence of each disorder. Some possible reasons that have been proposed for the relationship between PTSD and SUD are self-medication of anxiety with drugs or alcohol, increased exposure to traumatic events due to activities involved in acquiring illegal substances, or addictive substances altering the brain's stress response systems to make users more vulnerable to PTSD. Yet another possibility is that some people have an intrinsic vulnerability that predisposes them to both PTSD and SUD. In this review, we integrate clinical and animal data to explore these possible etiological links between SUD and PTSD, with an emphasis on interactions between dopaminergic, adrenocorticotropic, GABAergic, and glutamatergic neurobehavioral mechanisms that underlie different emotional learning styles.

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“…As with preclinical research on sex differences in relation to EtOH drinking, there is also a paucity of preclinical research on sex differences in relation to affective behavior. In regard to exploratory and anxiety-like behavior, most research has been conducted in Wistar and Sprague-Dawley rats, and has found that females compared to males show greater horizontal and vertical (rearing) activity in a novel chamber (Hughes & Hancock, 2016;Kokras et al, 2020), greater or no difference in time in the light chamber of a light-dark box (De Oliveira Sergio et al, 2021;Fleming et al, 2019;Kokras et al, 2020), and more hole exploration in a hole board apparatus (Kokras et al, 2020;Ray & Hansen, 2004). One study has probed the sexdependent effects of EtOH on behavior in a light-dark box, using experimenter-administered EtOH, and found that this EtOH reduced to an equal extent time spent in the light chamber, entries into the light chamber, and overall ambulatory activity in male and female rats (Fleming et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

“…In regard to exploratory and anxiety‐like behavior, most research has been conducted in Wistar and Sprague‐Dawley rats, and has found that females compared to males show greater horizontal and vertical (rearing) activity in a novel chamber (Hughes & Hancock, 2016; Kokras et al, 2020), greater or no difference in time in the light chamber of a light–dark box (De Oliveira Sergio et al, 2021; Fleming et al, 2019; Kokras et al, 2020), and more hole exploration in a hole board apparatus (Kokras et al, 2020; Ray & Hansen, 2004). One study has probed the sex‐dependent effects of EtOH on behavior in a light–dark box, using experimenter‐administered EtOH, and found that this EtOH reduced to an equal extent time spent in the light chamber, entries into the light chamber, and overall ambulatory activity in male and female rats (Fleming et al, 2019). To our knowledge, no such investigations of sex‐dependent effects of EtOH have been made of behavior in a novel chamber or hole board apparatus nor has exploratory behavior after voluntary EtOH drinking been examined.…”

Section: Introductionmentioning

confidence: 99%

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

Pirino

Martin

Carpenter

et al. 2022

Alcoholism Clin & Exp Res

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Background While men in the United States consume more alcohol than women, rates of drinking are converging. Nevertheless, females remain underrepresented in preclinical alcohol research. Here, we examined rats' sex‐related differences in patterns of ethanol (EtOH) drinking and the effects of this drinking on exploratory and anxiety‐like behavior. Methods Adult male and female Long‐Evans rats were given 20% ethanol under the intermittent‐access two‐bottle‐choice paradigm. Their intake was measured daily for the first 7 weeks. During the eighth week, intake was measured over the 24 h of daily access. During the ninth week, they, along with EtOH‐naive controls, were tested prior to daily access in a novel chamber, light–dark box, and hole board apparatus. During the tenth week, blood ethanol concentration (BEC) was assessed after 30 to 40 min of access. Results Females overall demonstrated higher ethanol intake and preference across all access weeks than males, although only half of females drank significantly more than males. Across 24 h of daily access, both sexes had their highest intake in the first 30 min and their lowest in the middle of the light phase of the light/dark cycle. Despite their greater ethanol intake, females did not show significantly different BECs than males. In behavioral tests, females showed less vertical time in a novel activity chamber, more movement between chambers in a light–dark box, and more nose pokes in a hole‐board apparatus than males. While a history of ethanol drinking led to a trend for lower vertical time in the activity chamber and greater chamber entries in the light–dark box, the effects were not sex‐dependent. Conclusions These results suggest that female and male rats could both be tested for acute effects of ethanol after 30 min of daily access, but that nuanced considerations are needed in the design of these experiments and the interpretation of their findings.

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Withdrawal from Brief Repeated Alcohol Treatment in Adolescent and Adult Male and Female Rats

Cited by 10 publications

References 55 publications

Effect of Estrous Cycle on Behavior of Females in Rodent Tests of Anxiety

Effect of Estrous Cycle on Behavior of Females in Rodent Tests of Anxiety

Mechanisms of Shared Vulnerability to Post-traumatic Stress Disorder and Substance Use Disorders

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

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