•MPH and METH effects on anxiety in females have not been previously studied.•Acute and chronic dosing was used to determine changes in anxiety during the EPM.•MPH, given acute or chronic, decreased ...anxiety in adult female rats.•METH and MPH altered locomotion during an open field test, but not during the EPM.•Adult female rats given MPH show evidence of an anxiolytic effect.
Methylphenidate (MPH) and methamphetamine (METH) are two commonly abused psychomotor stimulants that impact anxiety, but in a manner that is currently unclear. This study adds to the literature by testing the effects of MPH and METH on anxiety in adult female rats, which has not previously been studied. In Experiment1, changes in anxiety-like behavior were determined using the Elevated Plus Maze (EPM) following either an acute injection of saline, METH (1 mg/kg), or MPH (10 mg/kg). Changes in general locomotion were measured using the open field test. MPH, but not METH, significantly decreased anxiety; MPH and METH were associated with increased activity in the open field. In Experiment2, we compared the effects of three once daily injections of saline to MPH (10 mg/kg) or METH (1 mg/kg). As with the acute dosing, repeated exposure to MPH, but not METH, decreased anxiety, and both drugs increased locomotion. Neither acute nor chronic dosing produced a change in locomotion during the EPM, indicating that the anxiolytic effects of MPH are independent of changes in locomotor behavior. These findings add further clarification to the literature investigating the psychoactive properties of MPH, with a special and needed emphasis on female behavior.
Astronauts on interplanetary missions - such as to Mars - will be exposed to space radiation, a spectrum of highly-charged, fast-moving particles that includes
Fe and
Si. Earth-based preclinical ...studies show space radiation decreases rodent performance in low- and some high-level cognitive tasks. Given astronaut use of touchscreen platforms during training and space flight and given the ability of rodent touchscreen tasks to assess functional integrity of brain circuits and multiple cognitive domains in a non-aversive way, here we exposed 6-month-old C57BL/6J male mice to whole-body space radiation and subsequently assessed them on a touchscreen battery. Relative to Sham treatment,
Fe irradiation did not overtly change performance on tasks of visual discrimination, reversal learning, rule-based, or object-spatial paired associates learning, suggesting preserved functional integrity of supporting brain circuits. Surprisingly,
Fe irradiation improved performance on a dentate gyrus-reliant pattern separation task; irradiated mice learned faster and were more accurate than controls. Improved pattern separation performance did not appear to be touchscreen-, radiation particle-, or neurogenesis-dependent, as
Fe and
Si irradiation led to faster context discrimination in a non-touchscreen task and
Fe decreased new dentate gyrus neurons relative to Sham. These data urge revisitation of the broadly-held view that space radiation is detrimental to cognition.
The present study characterized the effects of ketamine on sexual behavior and anxiety in female rats. In Experiment 1, female subjects received an injection of ketamine (10.0mg/kg) or saline 30min ...prior to a sexual partner-preference test during which each female subject was given the opportunity to interact with a female stimulus or a sexually vigorous male stimulus. Immediately afterwards, female subjects were tested for locomotion in an open field test. Ketamine-treated subjects spent significantly more time with the male stimulus than saline-treated subjects. No other measures of mating behavior (i.e., paced mating behavior, lordosis) were affected by ketamine. Ketamine also had no effect on locomotion. In Experiment 2, female subjects received an injection of ketamine (10.0mg/kg), or saline daily for 10days to investigate the possibility that sexual dysfunction emerges only after repeated exposure. Similar to the results of Experiment 1, ketamine-treated subjects spent significantly more time with the male stimulus than saline-treated subjects. Chronic ketamine treatment also decreased the likelihood of leaving the male after mounts, without affecting any other measures of sexual behavior. Chronic ketamine had no effect on locomotion. In Experiment 3, female subjects received an injection of ketamine (10.0mg/kg) or saline and were tested for anxiety in an elevated plus maze test and for locomotion in an open field test. Acute ketamine had no effect on anxiety or locomotion. In Experiment 4, female subjects received an injection of ketamine (10.0mg/kg) or saline daily for 10days to investigate the possibility that anxiety emerges only after repeated exposure. Chronic ketamine exposure had no effect on any measure of anxiety. However, chronic ketamine exposure increased locomotion. The results from these experiments indicate that unlike other medications prescribed for depression, neither acute nor chronic ketamine treatment causes anxiety or disruption of sexual behavior.
•An acute dose of ketamine (10.0mg/kg i.p.) did not disrupt sexual behavior in female rats.•An acute dose of ketamine increased time spent with the male stimulus during a sexual partner-preference test.•Daily administration of ketamine (10.0mg/kg i.p.) for 10days did not disrupt sexual behavior in female rats.•Chronic ketamine administration increased time spent with the male stimulus during a sexual partner-preference test.•Neither acute nor chronic ketamine administration affected anxiety-like behavior in an elevated plus maze test.
Astronauts traveling to Mars will be exposed to chronic low doses of galactic cosmic space radiation, which contains highly charged, high-energy (HZE) particles. 56Fe-HZE-particle exposure decreases ...hippocampal dentate gyrus (DG) neurogenesis and disrupts hippocampal function in young adult rodents, raising the possibility of impaired astronaut cognition and risk of mission failure. However, far less is known about how exposure to other HZE particles, such as 28Si, influences hippocampal neurogenesis and function. To compare the influence of 28Si exposure on indices of neurogenesis and hippocampal function with previous studies on 56Fe exposure, 9-week-old C57BL/6J and Nestin-GFP mice (NGFP; made and maintained for 10 or more generations on a C57BL/6J background) received whole-body 28Si-particle-radiation exposure (0, 0.2 and 1 Gy, 300 MeV/n, LET 67 KeV/μ, dose rate 1 Gy/min). For neurogenesis assessment, the NGFP mice were injected with the mitotic marker BrdU at 22 h postirradiation and brains were examined for indices of hippocampal proliferation and neurogenesis, including Ki67+, BrdU+, BrdU+NeuN+ and DCX+ cell numbers at short- and long-term time points (24 h and 3 months postirradiation, respectively). In the short-term group, stereology revealed fewer Ki67+, BrdU+ and DCX+ cells in 1-Gy-irradiated group relative to nonirradiated control mice, fewer Ki67+ and DCX+ cells in 0.2 Gy group relative to control group and fewer BrdU+ and DCX+ cells in 1 Gy group relative to 0.2 Gy group. In contrast to the clearly observed radiation-induced, dose-dependent reductions in the short-term group across all markers, only a few neurogenesis indices were changed in the long-term irradiated groups. Notably, there were fewer surviving BrdU+ cells in the 1 Gy group relative to 0- and 0.2-Gy-irradiated mice in the long-term group. When the short- and long-term groups were analyzed by sex, exposure to radiation had a similar effect on neurogenesis indices in male and female mice, although only male mice showed fewer surviving BrdU+ cells in the long-term group. Fluorescent immunolabeling and confocal phenotypic analysis revealed that most surviving BrdU+ cells in the long-term group expressed the neuronal marker NeuN, definitively confirming that exposure to 1 Gy 28Si radiation decreased the number of surviving adult-generated neurons in male mice relative to both 0- and 0.2-Gy-irradiated mice. For hippocampal function assessment, 9-week-old male C57BL/6J mice received whole-body 28Si-particle exposure and were then assessed long-term for performance on contextual and cued fear conditioning. In the context test the animals that received 0.2 Gy froze less relative to control animals, suggesting decreased hippocampal-dependent function. However, in the cued fear conditioning test, animals that received 1 Gy froze more during the pretone portion of the test, relative to controls and 0.2-Gy-irradiated mice, suggesting enhanced anxiety. Compared to previously reported studies, these data suggest that 28Si-radiation exposure damages neurogenesis, but to a lesser extent than 56Fe radiation and that low-dose 28Si exposure induces abnormalities in hippocampal function, disrupting fear memory but also inducing anxiety-like behavior. Furthermore, exposure to 28Si radiation decreased new neuron survival in long-term male groups but not females suggests that sex may be an important factor when performing brain health risk assessment for astronauts traveling in space.
The present study characterized the effects of weekly ketamine injections on sexual behavior and anxiety in female and male rats, using a dosing protocol that mimics human therapeutic treatment for ...depression. In Experiment 1A, ketamine (10 mg/kg, i.p.) or saline was injected once per week for four consecutive weeks. The partner preference paradigm was used to measure sexual motivation 30 min after each weekly injection. Briefly, subjects were first given a 10-min test during which they could choose to spend time in the vicinity of a sexually receptive female stimulus or a sexually experienced male stimulus, however physical contact was restricted (no-contact). Immediately after, subjects were given unrestricted access to the stimulus animals (contact). After a washout period, subjects received four additional weekly injections of ketamine or saline, and then were tested for anxiety-like behavior on the elevated plus maze (EPM) after the last injection (Experiment 1B). For Experiment 2, similar procedures were used to test the effects of weekly ketamine injections on sexual motivation (Experiment 2A) and anxiety (Experiment 2B) in male subjects. In female subjects, ketamine increased sexual motivation as measured by greater time spent with the male stimulus, decreased likelihood of leaving after receiving mounts, and shorter return latencies after receiving intromissions, when compared to saline controls. In male subjects, ketamine shortened latency to first mount and first intromission, as well as increased time spent with the female stimulus. Very little anxiety was observed in either group (ketamine or saline) of female or male subjects when tested on the EPM. In conclusion, even after four weeks of ketamine exposure, sexual dysfunction did not emerge in either females or males. In contrast, ketamine increased sexual motivation in both females and males, with an initial robust response. However, as both groups gained sexual experience, the impact of ketamine diminished.
•Ketamine enhanced sexual behavior and sexual motivation in female rats when dosing protocol mimics human dosing.•Ketamine enhanced copulatory behavior and sexual motivation in male rats.•Effects of ketamine on sexual behavior were mostly limited to initial mating tests.•As rats gained sexual experience, effects of ketamine diminished.•Ketamine had minimal effect on anxiety.
Astronauts traveling to Mars will be exposed to chronic low doses of galactic cosmic space radiation, which contains highly charged, high-energy (HZE) particles.
Fe-HZE-particle exposure decreases ...hippocampal dentate gyrus (DG) neurogenesis and disrupts hippocampal function in young adult rodents, raising the possibility of impaired astronaut cognition and risk of mission failure. However, far less is known about how exposure to other HZE particles, such as
Si, influences hippocampal neurogenesis and function. To compare the influence of
Si exposure on indices of neurogenesis and hippocampal function with previous studies on
Fe exposure, 9-week-old C57BL/6J and Nestin-GFP mice (NGFP; made and maintained for 10 or more generations on a C57BL/6J background) received whole-body
Si-particle-radiation exposure (0, 0.2 and 1 Gy, 300 MeV/n, LET 67 KeV/μ, dose rate 1 Gy/min). For neurogenesis assessment, the NGFP mice were injected with the mitotic marker BrdU at 22 h postirradiation and brains were examined for indices of hippocampal proliferation and neurogenesis, including Ki67
, BrdU
, BrdU
NeuN
and DCX
cell numbers at short- and long-term time points (24 h and 3 months postirradiation, respectively). In the short-term group, stereology revealed fewer Ki67
, BrdU
and DCX
cells in 1-Gy-irradiated group relative to nonirradiated control mice, fewer Ki67
and DCX
cells in 0.2 Gy group relative to control group and fewer BrdU
and DCX
cells in 1 Gy group relative to 0.2 Gy group. In contrast to the clearly observed radiation-induced, dose-dependent reductions in the short-term group across all markers, only a few neurogenesis indices were changed in the long-term irradiated groups. Notably, there were fewer surviving BrdU
cells in the 1 Gy group relative to 0- and 0.2-Gy-irradiated mice in the long-term group. When the short- and long-term groups were analyzed by sex, exposure to radiation had a similar effect on neurogenesis indices in male and female mice, although only male mice showed fewer surviving BrdU
cells in the long-term group. Fluorescent immunolabeling and confocal phenotypic analysis revealed that most surviving BrdU
cells in the long-term group expressed the neuronal marker NeuN, definitively confirming that exposure to 1 Gy
Si radiation decreased the number of surviving adult-generated neurons in male mice relative to both 0- and 0.2-Gy-irradiated mice. For hippocampal function assessment, 9-week-old male C57BL/6J mice received whole-body
Si-particle exposure and were then assessed long-term for performance on contextual and cued fear conditioning. In the context test the animals that received 0.2 Gy froze less relative to control animals, suggesting decreased hippocampal-dependent function. However, in the cued fear conditioning test, animals that received 1 Gy froze more during the pretone portion of the test, relative to controls and 0.2-Gy-irradiated mice, suggesting enhanced anxiety. Compared to previously reported studies, these data suggest that
Si-radiation exposure damages neurogenesis, but to a lesser extent than
Fe radiation and that low-dose
Si exposure induces abnormalities in hippocampal function, disrupting fear memory but also inducing anxiety-like behavior. Furthermore, exposure to
Si radiation decreased new neuron survival in long-term male groups but not females suggests that sex may be an important factor when performing brain health risk assessment for astronauts traveling in space.
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