Sexually dimorphic MK801-induced c-fos in the rat hypothalamic paraventricular nucleus.

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.

The effect of lactation on induced Fos-like immunoreactivity in the rat hypothalamic paraventricular nucleus.

Lactating rats display a period of blunted hypothalamo-pituitary-adrenal (HPA) response to a variety of stressors. This hyporesponsiveness is reported to be dependent upon continuous mother-pup interactions. In this study, computer-assisted densitometric methods were used to measure levels of induced Fos-like immunoreactivity (FLI) in the hypothalamic paraventricular nucleus (PVN) of lactating and non-lactating rats. Adrenalectomy (ADX) induces elevated levels of FLI in the PVN of non-lactating rats. We have observed that, between post-partum day (pd) 4 and pd 21, the level of ADX-induced FLI in the PVN of lactating rats follows a U-shaped distribution; that the persistence of this phenomenon is dependent upon continued mother-pup interaction and that sustained mother-pup interaction beyond the end of the normal suckling period (pd 21) does not extend the period of refractoriness. We have further determined that both the non-specific neural activator Metrazole, and the glutamate agonist N-methyl-D,L-aspartate (NMA), induced smaller increases in FLI in the PVN of lactating rats compared to non-lactating cohorts, and that the suppressing effect of lactation on Metrazole-induced FLI does not extend to all brain regions. These results suggest that mechanisms responsible for the onset and maintenance of the so-called lactational stress-hyporesponsive period (LSHRP) include altered function of glutamatergic pathways.

Anomalous adrenalectomy-induced Fos-like immunoreactivity in the hypothalamic paraventricular nucleus of stress-hyporesponsive rats.

Cellular activity in the paraventricular nucleus of the hypothalamus (PVN) in response to adrenalectomy (ADX) and sham-ADX was measured in adult male rats, lactating females, and nursing pups using c-fos immunocytochemistry. Increased Fos-like immunoreactivity (FLI) was seen in the PVN of male rats at 4 h following ADX or sham-ADX but this increase was transient, and basal values were restored within 24 h. In suckling pups, ADX induced a marked FLI response in the PVN at 3 days and at 18 days postpartum. At 11 days postpartum, however, the FLI response was attenuated relative to adult animals, and 3- and 18-day-old pups. Similarly, in nursing mothers, ADX induced FLI at 3 days, but this response disappeared by 7 days and did not reappear by the end of the suckling period (day 21). These data indicate that c-fos expression is a sensitive indicator of hyporesponsiveness in the hypothalamic-pituitary-adrenal (HPA) system.