Characterization of a uterine-type oxytocin receptor in the rat hippocampus.

Abstract

Extracellular recordings were obtained from a class of nonpyramidal neurones in hippocampal slices. Oxytocin applied to the bath at concentrations of 1 nM or greater excited these cells. This effect was reversibly antagonized by a synthetic structural analogue known to block the peripheral endocrine effects of oxytocin. The effect of oxytocin was mimicked by a selective oxytocic agonist and, with less potency, by vasopressin and by other structural analogues. The potencies of oxytocin, vasopressin, and of these analogues in the hippocampus correlated well with their uterotonic activities but not with their vasopressor or antidiuretic activities. The data suggest that a class of hippocampal neurones is endowed with receptors for oxytocin that are similar to those of uterine smooth muscle cells.Vasopressin and oxytocin are peptide hormones that are synthesized in neuronal cell bodies located in the hypothalamus and are carried by axoplasmic transport to the neurohypophysis, from which they are released into the general circulation in response to appropriate stimuli. In addition, they are also present in nerve fibers in various areas within the central nervous system (1). A calcium-dependent, depolarization-induced release of these peptides can be demonstrated from some areas of the brain where axons immunoreactive for vasopressin and oxytocin have been shown to terminate synaptically on neuronal elements (2, 3). This suggests that oxytocin and vasopressin, in addition to their general hormonal effects, might act as neurotransmitters or neuromodulators in the brain.It has been shown that vasopressin and oxytocin increase the rate of firing of a class of neurones in the CAl area of hippocampal slices. This electrophysiological response was not due to the peptides interacting with a receptor resembling the renal antidiuretic vasopressin receptor (4). However, at least two other types of endocrine receptors for neurohypophyseal hormones have been recognized. One is the vasopressor receptor, present on vascular smooth muscle cells and on liver cells, which triggers the vasopressor and glycogenolytic effects of vasopressin in these tissues (5-8). The other is an oxytocic receptor (9), which triggers the contractile response of the uterus to oxytocin. In this study, we attempted to assess whether receptors for oxytocin and vasopressin are similar in such widely different parts of the body as the brain and peripheral tissues responsive to these hormones. Because both vasopressin and oxytocin excited hippocampal neurones, it was possible that oxytocic receptors, vasopressor receptors, or a mixed novel class of receptors for neurohypophyseal peptides were involved. In theory, it should be possible to elucidate this point by using specific vasopressor antagonists and oxytocic antagonists. However, available antagonists are not truly specific and act on both vasopressor and oxytocic receptors (10). In contrast, highly selective oxytocic agonists are available (11). Therefore, we used a number of compounds possessing ...

Septal and Hippocampal Release of Oxytocin, but not Vasopressin, in the Conscious Lactating Rat During Suckling

“…OXT meets many of the criteria which are usually applied to assign a role as neurotransmitter or neuromodulator to a given compound, including its localization within presynaptic vesicles (33,34), its calcium-and veratridine-dependent central release (1 I , 13), the presence of specific binding sites (35,36) and its effects on electrical activity of target neurons (37,38). All these criteria are met in relation to the septum and hippocampus.…”

Oxytocin Attenuates Stress-Induced c-fosmRNA Expression in Specific Forebrain Regions Associated with Modulation of Hypothalamo–Pituitary–Adrenal Activity

“…Widespread neuronal activation was detected throughout the hippocampal formation in response to restraint, similar to previous studies (Melia et al, 1994;Chowdhury et al, 2000). Oxytocin binding sites (Freund-Mercier et al, 1987) and oxytocin-sensitive neurons (Mühlethaler et al, 1983;Zaninetti and Raggenbass, 2000) are present in the hippocampus, and it is possible that they may exert an action through modulation of the well established glucocorticoid negative feedback pathway. Indeed, it has been shown that oxytocin receptors within the hippocampus are upregulated by stress, perhaps representing a negative feedback loop within the system (Liberzon and Young, 1997).…”

Learning About Oxytocin: Pharmacologic and Behavioral Issues

“…A number of studies of the effect of OT on basal neurotransmission in adult hippocampus have found an inhibitory action mediated by the activation of GABAergic interneurons (89)(90)(91)(92), and a few studies have also found that OT acts on activity-dependent hippocampal synaptic plasticity. In the medial prefrontal cortex, OT converts long-term depression to long-term potentiation (LTP) (93), and in the cornu ammonis 1 (CA1) pyramidal neurons of adult rats, it prolongs the duration of LTP (10,94).…”