Lactation inhibits hippocampal and cortical activation of cFos expression by nivida but not kainate receptor agonists

doi:10.1016/1044-7431(92)90044-3

Molecular and Cellular Neuroscience

Volume 3, Issue 3, June 1992, Pages 244-250

https://doi.org/10.1016/1044-7431(92)90044-3 Get rights and content

Abstract

Lactation in the rat activates afferent neuronal pathways that cause marked changes in hormone secretion and maternal behavior. Previously, we used excitatory amino acids (EAAs) to challenge the neuroendocrine axis of the lactating rat and showed altered hypothalamic responsiveness to EAAs. In conducting those studies, we noted that the typical hyperactive behavior associated with NMA (N-methyl-d,l-aspartate) treatment was completely absent in lactating animals. In these studies we have examined the effects of lactation on cortical responsiveness to EAAs by using cFos expression as a marker of neuronal activation. Lactation inhibited hippocampal and cortical cFos induction in response to NMA, which was consistent with the absence of behavioral responses. However, NMA responsiveness was observed in other areas of the brain. Recovery of cortical activation in response to NMA was not observed until 24 h after removal of the suckling stimulus. In contrast, treatment with kainate (an agonist for a different type of glutamate receptor) induced similar patterns of cFos expression and behavioral responses (wet-dog shakes) in cycling and lactating rats. These data demonstrate that lactation, a physiological condition, can inhibit cortical activation that is mediated by NMDA but not kainate receptors. In so doing, lactation represents a novel model system in which to study mechanisms of NMDA receptor inactivation and subsequent consequences on hippocampal and cortical function.

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The relationship between endogenous gonadal steroid levels and persistent or chronic pain is poorly understood. These studies used an inflammation model to examine the role of the gonadal steroid, progesterone, in the development of persistent pain and hyperalgesia in lactating ovary-intact and ovariectomized rats. The results indicate that constant high plasma levels of progesterone attenuate inflammatory hyperalgesia by a mechanism involving inhibition of N-methyl-d-aspartate receptor activation at the spinal cord level. Since the pattern of high progesterone in lactating rats mimics the progesterone component of the luteal phase of the human menstrual cycle, these findings have significance in persistent or chronic pain conditions that are most prevalent in females.
Neural populations in the rat forebrain and brainstem activated by the suckling stimulus as demonstrated by cFos expression
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During lactation in the rat, the suckling stimulus plays an important role in mediating alterations in hypothalamic neuroendocrine function associated with lactation. To provide the basis for understanding the neural circuitry that may transmit suckling-induced signals into the hypothalamus, the present study used the expression of the immediate-early gene product, cFos protein, as a marker for neuronal activation to identify neural populations in the brain of lactating female rats activated by the suckling stimulus. In addition, cFos expression induced by the exteroceptive sensory stimuli (olfactory, auditory, visual) associated with pup exposure alone was also determined. Thus, cFos patterns in response to the physical suckling stimulus, which would include exteroceptive sensory stimuli associated with pup exposure, were compared with the patterns induced in response to pup exposure alone, so that neuronal populations specifically activated by the suckling stimulus could be identified. After 90 min of suckling, several forebrain areas, including the lateral septum, medial preoptic area, periventricular preoptic area and supraoptic nucleus of hypothalamus, showed a significant increase in cFos expression, compared with non-suckled controls and pup exposure animals. In addition, in the bed nucleus of stria terminalis, the medial amygdala and several cortical areas, cFos-positive cells were found in both suckling and pup exposure animals. In the brainstem, the suckling stimulus induced a significant increase in cFos expression in the ventrolateral medulla, locus coeruleus, lateral parabrachial nucleus, lateral and ventrolateral portions of the caudal part of the periaqueductal gray, and caudal portion of the paralemniscal nucleus, compared with non-suckled controls and pup exposure animals. As expected, in several areas related with sensory input, such as reticular formation and pontine nucleus, cFos expression was found in both suckling and pup exposure animals. Moreover, when double-label immunocytochemistry was used to identify cFos- and catecholamine-positive neurons in the brainstem, it was found that catecholamine-positive neurons in the ventrolateral medulla and locus coeruleus showed a significant increase in cFos expression in response to suckling compared with non-resuckled and pup-exposure groups.
Using cFos expression as a marker for neuronal activation, the present studies identified the neural populations in the brain that are activated by the suckling stimulus. By comparing the pattern of cFos expression observed in response to pup exposure alone or the suckling stimulus, the present studies differentiated the neural populations activated by the physical suckling stimulus from the populations activated by the exteroceptive sensory stimuli associated with pup exposure. These suckling-activated areas are likely candidates for playing an important role in transmitting the effects of the suckling stimulus into the hypothalamus to regulate neuroendocrine alterations associated with lactation.
Resistance of the hippocampus in the lactating rat to N-methyl-D- aspartate (NMDA)-mediated excitation is not due to a nonfunctional receptor system
1998, Brain Research
The lactating rat has been shown to lack a behavioral response and immediate early gene expression (cFos) in the hippocampus (Hipc) following intravenous or intracerebroventricular administration of an N-methyl-d-aspartate (NMDA) receptor agonist. The purpose of this study is to determine whether neurons in the Hipc have an intact postsynaptic NMDA receptor system. The presence of NMDA receptor protein was determined by Western blot analysis for the NR1, NR2A, and NR2B subunits. The presence of functional NMDA receptors in the Hipc was determined by behavioral responses and the expression of cFos immunoreactivity (-ir) in response to microinjection of an NMDA receptor agonist into the hilus of the dentate gyrus. No difference in NR1 and NR2A subunit protein in the Hipc was detected between the lactating and nonlactating rats. However, there was a 26% decrease in NR2B subunit protein in this region in the lactating rat. Lactating rats receiving NMA injections displayed hyperactive behavior, similar to that observed in the nonlactating animals receiving the same treatment. The lactating rat and the nonlactating rat also displayed equivalent bilateral cFos-ir in the dentate gyrus (DG), CA1 and CA3 regions of the Hipc in response to unilateral NMA injections into the Hipc. These data indicate that the lactating rat has an intact postsynaptic NMDA receptor system. Thus, Hipc refractoriness to peripheral and third ventricular injections of an NMDA receptor agonist may reflect inhibition of presynaptic input and glutamate release.

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^☆: Supported by NIH Grants HD-14643 and NS-28730.

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Lactation inhibits hippocampal and cortical activation of cFos expression by nivida but not kainate receptor agonists☆

Abstract

Neuron

Biochem. Biophys. Res. Commun

J. Biol. Chem

TIPS

Peptides

Brain Res

Neuroscience

Brain Res

Brain Res

Milk ejection and its control

Maternal behavior

Qualitative changes in Luteinizing hormone and prolactin responses to N-methyl-d-aspartic acid during lactation in the rat

Endocrinology

Luteinizing hormone-releasing hormone neurons express Fos protein during the proestrous surge of luteinizing hormone

Expression of cFos protein in brain: Metabolic mapping at the cellular level

Science

Stimulation of neuronal acetyl choline receptors induces rapid gene transcription

Science

Mapping patterns of c-Fos expression in the central nervous system after seizure

Science