Sex differences in the actions of psychoactive agents and progesterone on anxiety-related behaviour in the mongolian gerbil (meriones unguiculatus) and the effects of corticosterone on the hippocampal morphology of wistar rats (rattus norvegicus)

Abstract

Many anxiety and stress-related disorders exhibit definitive sex differences in their prevalence, symptomology, response to treatment and prognosis. Animal studies have increased the understanding of these disorders, but much of the current research in this area has been conducted using only male rats or mice. Thus, the investigation of sex differences, especially within other rodent species is still relatively ignored. There is much evidence to implicate the involvement of steroid hormones in the response to anxiety and stress. The neuroactive steroid progesterone has been associated with the
regulation of anxiety behaviour in rodents, whilst the steroid corticosterone has been related to the damaging effects of stress, especially within the hippocampus. However, current investigations have failed to examine the influence of gender on these findings.
The initial aim of this thesis was to evaluate the suitability of the elevated plus-maze and black-white box tests of anxiety for male and female Mongolian gerbils. The second part of this thesis then evaluates the behavioural effects of progesterone
treatment and withdrawal in this species. Finally, this thesis evaluates the influence of chronic corticosterone treatment on hippocampal volume and astrocyte cell numbers in male and female rats. Pharmacological validation of the elevated plus-maze and blackwhite box revealed that diazepam produced similar anxiolysis in male and female gerbils. Buspirone appeared to modulate motor activity rather that anxiety-specific behaviours in both sexes, but to a greater extent in males. Caffeine administration induced anxiety in both tests, but was more prominent in male gerbils. FG7142 also demonstrated some anxiogenic activity, however, this increase in anxiety was represented by different behavioural alterations in each sex. Investigation of the behavioural effects of progesterone treatment revealed that acute and chronic administration produced only weak effects on anxiety-related behaviour. Even so, acute progesterone appeared to produce greater anxiolysis in females, whereas these sex differences in treatment response were abolished by chronic treatment. Withdrawal of chronic progesterone appeared to increase anxiety in both the elevated plus-maze and black-white box, and was comparable for males and females. Examination of the effects of chronic corticosterone in rats revealed no significant alteration in the volume of the hippocampus in either sex, although male rats had larger hippocampal volume than females. Prolonged corticosterone treatment did produce increases in hippocampal astrocyte numbers in specific hippocampal regions. The findings of these investigations are discussed in relation to the aetiology of anxiety disorders and stress-related
hippocampal damage.