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Sexually dimorphic MK801-induced c-fos in the rat hypothalamic paraventricular nucleus
N Wintrip1, D M Nance, M Wilkinson
1Department of Physiology and Biophysics, Dalhousie University, Faculty of Medicine, Halifax, NS, Canada.
Abstract:
MK801 induces Fos-like immunoreactivity (FLI) in the paraventricular nucleus (PVN) in a sex, age, hormone and dosage dependent manner. MK801 (1.0 mg/kg) elicited greater behavioural disruption, but less FLI in the PVN of cycling and lactating female rats, compared to like-treated males. Results from gonadectomized rats with or without acute steroid replacement resembled those seen in intact rats but sex differences were extinguished. At a lower dose (0.1 mg/kg), behavioural effects were diminished but females exhibited more behavioural disruption. At this dose however, more FLI was seen in the PVN of females compared to males, but only male-lactating female differences were significant. Taken together, the data suggest that the action of MK801 on the PVN is influenced by gonadal steroids.
Insights
MK-801
Area of Science:
- Neuroscience
- Endocrinology
- Pharmacology
Background:
- The paraventricular nucleus (PVN) is a key brain region involved in stress and behavioral responses.
- The NMDA receptor antagonist MK-801 is known to affect behavior and neuronal activity.
Purpose of the Study:
- To investigate the influence of sex, age, hormones, and dosage on MK-801-induced Fos-like immunoreactivity (FLI) in the PVN.
- To determine the role of gonadal steroids in mediating the effects of MK-801 on PVN activity and behavior.
Main Methods:
- Administration of MK-801 at different dosages (1.0 mg/kg and 0.1 mg/kg) to male and female rats.
- Assessment of behavioral disruption and Fos-like immunoreactivity (FLI) in the PVN.
- Utilizing gonadectomized rats with and without steroid replacement to examine hormonal influences.
Main Results:
- MK-801 induced FLI in the PVN in a sex, age, hormone, and dosage-dependent manner.
- At 1.0 mg/kg, MK-801 caused greater behavioral disruption but less PVN FLI in females compared to males.
- Sex differences in PVN FLI were abolished in gonadectomized rats, suggesting a role for gonadal steroids.
Conclusions:
- Gonadal steroids significantly influence the action of MK-801 on the paraventricular nucleus.
- The observed sex differences in MK-801's effects are mediated, at least in part, by gonadal steroid levels.