Sex differences in the elevated plus-maze test and large open field test in adult Wistar rats.

There is a growing need for a better understanding of sex differences in animal models of psychiatric disorders. The elevated plus-maze (EPM) test and large open field (LOF) test are widely used to study anxiety-like behavior in rodents. Our studies explored sex differences in anxiety and activity parameters in the LOF and EPM and determined whether these parameters correlate within and between tests. Drug naïve adult male and female Wistar rats (n = 47/sex) were used for the studies, and the rats were tested for 5 min in the EPM and 10 min in the LOF. The females spent more time on the open arms of the EPM and made more open arms entries than the males. The females also spent more time in the center zone of the LOF and made more center zone entries. The females traveled a greater distance in the LOF and EPM. There was a moderate positive correlation between time on the open arms of the EPM and time in the center zone of the LOF. There was also a moderate positive correlation between open arms entries in the EPM and center zone entries in the LOF. A hierarchical cluster analysis revealed one cluster with LOF parameters, one cluster with EPM parameters, and one cluster with parameters related to the avoidance of open spaces. In conclusion, these findings indicate that female rats display less anxiety-like behavior in the EPM and LOF. Furthermore, there are sex differences for almost all behavioral parameters in these anxiety tests.

Sex differences in the reward deficit and somatic signs associated with precipitated nicotine withdrawal in rats.

Female smokers are more likely to relapse than male smokers, but little is known about sex differences in nicotine withdrawal. Therefore, male and female rats were prepared with minipumps that contained nicotine or saline and sex differences in precipitated and spontaneous nicotine withdrawal were investigated. The intracranial self-stimulation (ICSS) procedure was used to assess mood states. Elevations in brain reward thresholds reflect a deficit in reward function. Anxiety-like behavior was investigated after the acute nicotine withdrawal phase in a large open field and the elevated plus maze test. The nicotinic receptor antagonist mecamylamine elevated the brain reward thresholds of the nicotine-treated rats but did not affect those of the saline-treated control rats. A low dose of mecamylamine elevated the brain reward thresholds of the nicotine-treated male rats but not those of the females. Mecamylamine also precipitated more somatic withdrawal signs in the nicotine-treated male than female rats. Minipump removal elevated the brain reward thresholds of the nicotine-treated rats for about 36 h but did not affect those of the saline-treated rats. There was no sex difference in the reward deficit during spontaneous nicotine withdrawal. In addition, the nicotine-treated male and female rats did not display increased anxiety-like behavior three to four days after minipump removal. In conclusion, these studies suggest that relatively low doses of a nicotinic receptor antagonist induce a greater reward deficit and more somatic withdrawal signs in male than female rats, but there is no sex difference in the reward deficit during spontaneous withdrawal.

Effects in rats of adolescent exposure to cannabis smoke or THC on emotional behavior and cognitive function in adulthood.

RATIONALE: Cannabis use is common among adolescents and some research suggests that adolescent cannabis use increases the risk for depression, anxiety, and cognitive impairments in adulthood. In human studies, however, confounds may affect the association between cannabis use and the development of brain disorders. OBJECTIVES: These experiments investigated the effects of adolescent exposure to either cannabis smoke or THC on anxiety- and depressive-like behavior and cognitive performance in adulthood in Long-Evans rats. METHODS: Adolescent rats of both sexes were exposed to either cannabis smoke from postnatal days (P) 29-49 or ascending doses of THC from P35-45. When the rats reached adulthood (P70), anxiety-like behavior was investigated in the large open field and elevated plus maze, depressive-like behavior in the sucrose preference and forced swim tests, and cognitive function in the novel object recognition test. RESULTS: Despite sex differences on some measures in the open field, elevated plus maze, forced swim, and novel object recognition tests, there were no effects of either adolescent cannabis smoke or THC exposure, and only relatively subtle interactions between exposure conditions and sex, such that sex differences on some performance measures were slightly attenuated. CONCLUSION: Neither cannabis smoke nor THC exposure during adolescence produced robust alterations in adult behavior after a period of abstinence, suggesting that adverse effects associated with adolescent cannabis use might be due to non-cannabinoid concomitants of cannabis use.