RESUMO
Ovarian hormones, such as estrogens and progesterone, are known to exert beneficial effects on cognition and some psychiatric disorders. The basis of these effects is not fully understood, but may involve altered cholinergic neurotransmission. This study aimed to investigate how a lack of ovarian hormones would impact muscarinic receptor-induced deficits in prepulse inhibition (PPI) and muscarinic receptor density in several brain regions. Adult female rats were either ovariectomized, to remove the source of ovarian hormones, or left intact (sham-operated). PPI is a measure of sensorimotor gating that is typically impaired in schizophrenia patients, and similar deficits can be induced in rats by administering scopolamine, a muscarinic receptor antagonist. Our results revealed no significant effects of ovariectomy on PPI after saline or scopolamine treatment. Autoradiography was performed to measure cholinergic muscarinic receptor binding density using [3H]-pirenzepine, [3H]-AF-DX, and [3H]-4-DAMP, to label M1, M2/M4, and M3 receptors, respectively. We examined the amygdala, caudate putamen, dorsal hippocampus, motor cortex, retrosplenial cortex, and ventromedial hypothalamus. There were no significant group differences in any region for any muscarinic receptor type. These results suggest that removing peripheral ovarian hormones does not influence the cholinergic muscarinic receptor system in the context of PPI or receptor binding density.
RESUMO
Sex differences are a prominent feature of the pathophysiology of psychiatric disorders, such as major depressive disorder, which affects women at a higher incidence than men. Research suggests that the most potent endogenous oestrogen, 17ß-oestradiol, may have therapeutic potential in treating depression. However, preclinical studies have produced mixed results, likely as a result of various methodological factors such as treatment duration. The present study aimed to investigate the effects of ovariectomy and chronic 17ß-oestradiol treatment via a s.c. silastic implant on behaviours relevant to depression in adult female Sprague-Dawley rats. Rats were assessed in the forced swim test, saccharin preference test and novel object recognition memory test, as well as for possible confounding behaviours, including locomotion and anxiety (open field test) and motivation and anxiety (novelty suppressed feeding test). Treatment effects were verified using body and uterus weight, as well as serum concentrations of 17ß-oestradiol, progesterone and testosterone. Compared to ovariectomised rats, chronic 17ß-oestradiol treatment enhanced saccharin preference and novel object recognition performance. There were no group differences in passive or active coping behaviour when assayed using the forced swim test. Taken together, these results support an antidepressant-like action of oestrogens but highlight that the beneficial effects of chronic 17ß-oestradiol treatment may be related to specific depression-related symptoms, particularly anhedonia and memory.
