Sex and age differences in locomotor and anxiety‐like behaviors in rats: From adolescence to adulthood

Bishnoi, Indra R.; Ossenkopp, Klaus‐Peter; Kavaliers, Martin

doi:10.1002/dev.22037

Cited by 52 publications

(42 citation statements)

References 85 publications

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“…Prior studies have identified sex differences in behavioral responding, as females display elevated motor activity compared to males in locomotor and anxiety-like assays [10][11][12].…”

Section: Discussionmentioning

confidence: 99%

“…The aforementioned research was primarily performed in male subjects, however increasing evidence highlights sex differences in behavioral responding. Across studies female subjects display augmented behavioral responses compared to males, including higher locomotor activity, faster latency, and elevated conditioned responding [10][11][12][13][14][15][16][17][18][19][20]. Furthermore, prior research has identified sex differences in dopamine neuron activity and release [21][22][23][24][25][26].…”

Section: Introductionmentioning

confidence: 99%

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Sex differences in behavioral responding and dopamine release during Pavlovian learning

Lefner

Dejeux

Wanat

2021

Preprint

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Learning associations between cues and rewards requires the mesolimbic dopamine system. The dopamine response to cues signals differences in reward value in well-trained animals. These value-related dopamine responses are absent during early learning when cues signal differences in the reward rate, which suggests cue-evoked dopamine release conveys differences between outcomes only after extensive training. However, it is unclear if this lack of value coding by cue-evoked dopamine release during early learning is unique to when cues signal differences in reward rate, or if this is also evident when cues signal differences in other value-related parameters such as reward size. To address this, we utilized a Pavlovian conditioning task in which one audio cue was associated with a small reward (one pellet) and another audio cue was associated with a large reward (three pellets). We performed fast-scan cyclic voltammetry to record changes in dopamine release in the nucleus accumbens of male and female rats throughout early learning. Cue-evoked dopamine release did not encode differences in reward value, and there were no differences in this response between males and females. However, female rats exhibited higher levels of conditioned responding and a faster latency to respond. Reward-evoked dopamine release scaled with reward size in both sexes, though there were transient sex differences in the dynamics of this response. We additionally identified sex differences in the number of post-reward head entries. Collectively these data illustrate sustained sex differences in behavioral responding as well as transient sex differences in reward-evoked dopamine release.

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“…Prior studies have identified sex differences in behavioral responding, as females display elevated motor activity compared to males in locomotor and anxiety-like assays [10][11][12].…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Sex differences in behavioral responding and dopamine release during Pavlovian learning

Lefner

Dejeux

Wanat

2021

Preprint

View full text Add to dashboard Cite

show abstract

“…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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“…Prior neurobehavioral studies suggest that the number of Hcrt neurons changes naturally throughout development 38 , along with changes in locomotor and anxiety-like behaviors 39 . There are only a few reports in any species examining both the brain and behavior at multiple stages of development 11 , 13 , and no studies of Hcrt neurons in adult subjects after embryonic EtOH exposure, only in young adolescent rats 35 and zebrafish 11 .…”

Section: Introductionmentioning

confidence: 99%

Sexually dimorphic and asymmetric effects of embryonic ethanol exposure on hypocretin/orexin neurons as related to behavioral changes in zebrafish

Collier

Yasmin

Khalizova

et al. 2021

Sci Rep

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Neurons expressing the neuropeptide hypocretin/orexin (Hcrt) in the hypothalamus promote reward-related behaviors including alcohol consumption and are shown in rodents and zebrafish to be stimulated by embryonic exposure to ethanol (EtOH). We used here in zebrafish three-dimensional analyses of the entire population of Hcrt neurons to examine how embryonic EtOH exposure at low-moderate concentrations (0.1% or 0.5% v/v) alters these neurons in relation to behavior. We found that EtOH in the water for 2 h (22–24 h post fertilization) increases the number of Hcrt neurons on the left but not right side of the brain through a stimulation of cell proliferation, this is accompanied by a decrease in locomotor activity under novel conditions but not after habituation, and these effects are evident in both larvae and adults indicating they are long lasting. Our analyses in adults revealed sexually dimorphic effects, with females consuming more EtOH-gelatin and exhibiting more freezing behavior along with an asymmetric increase in Hcrt neurons and males exhibiting increased aggression with no change in Hcrt. These findings suggest that a long lasting, asymmetric increase in Hcrt neurons induced by EtOH results from an asymmetric increase in proliferation specific to Hcrt and contributes to behavioral changes in females.

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Sex and age differences in locomotor and anxiety‐like behaviors in rats: From adolescence to adulthood

Cited by 52 publications

References 85 publications

Sex differences in behavioral responding and dopamine release during Pavlovian learning

Sex differences in behavioral responding and dopamine release during Pavlovian learning

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

Sexually dimorphic and asymmetric effects of embryonic ethanol exposure on hypocretin/orexin neurons as related to behavioral changes in zebrafish

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