J. was much smaller, and was enhanced in the presence of bicuculline. The GABAA receptor agonist muscimol also induced oxytocin release from supraoptic nuclei in young rats, but experienced no effect in adult rats. Oxytocin cells isolated from young rats showed an increase in [Ca2+]i in response to both allopregnanolone and muscimol. Allopregnanolone experienced no effect on [Ca2+]i or around the release of oxytocin or vasopressin from neurohypophysial axon terminals in CD123 either young or aged rats. We conclude that, in very young rats, (i) neurosteroids induce oxytocin release from your supraoptic nucleus by a mechanism that partly depends on the presence of GABA, which in young rats is usually depolarising to oxytocin cells, and which also partly depends upon endogenous oxytocin, and (ii) the effect of allopregnanolone SSR240612 upon oxytocin release changes with age, as the functional activity of GABAA receptors changes from excitation to inhibition of oxytocin cells. The magnocellular neurones of the hypothalamic supraoptic and paraventricular nuclei project to the neurohypophysis where they release oxytocin or vasopressin into the bloodstream. In addition, oxytocin and vasopressin are released from your cell body and dendrites of these neurones (Ludwig, 1998). This central release occurs semi-independently of release from your axon terminals (Ludwig 2002), and appears to be involved in pre- and post-synaptic regulation of electrical activity (Brussaard 1996; Kombian 1997) via specific receptors whose activation results in an increase in intracellular calcium ([Ca2+]i) (Dayanithi 1996). Central (somato-dendritic) peptide release is also involved in the striking physiologically regulated reorganisation of cellular architecture of the nuclei (Theodosis 1986). The striking morphological plasticity during parturition and lactation is mainly attributable to central oxytocin release (Theodosis 1986), but it is also influenced by steroid hormones (Montagnese 1990). Steroid hormones are potent neuronal modulators that are synthesised by glial cells (Garcia-Segura 1995; Baulieu, 1997) and by some neuronal populations (Sakamoto 2001), as well as deriving from peripheral sources. In addition to their genomic effects, neurosteroids display non-genomic effects in neurones, ranging from modulation of firing rate and neurotransmitter release, induction of sedation, anaesthesia and behavioural changes (Spindler, 1997; Wakerley & Richardson, 1998; McEwen & Alves, 1999; Toran-Allerand 1999; Israel & Poulain, 2000; Leng, 2000). These effects are mediated either by specific receptors or by allosteric modulation of major ligand-gated ion channels such as the GABAA receptor (Twyman & Macdonald, 1992) or the NMDA receptor (Lambert 1995; Rupprecht & Holsboer, 1999; Falkenstein 2000). In 1995, Wang and colleagues exhibited that oestradiol could induce acute exocytosis of oxytocin and vasopressin from your dendrites of adult hypothalamic neurones, but experienced no effect on release from neurohypophysial axon terminals (Wang 1995). In fetal rat hypothalamic neurones, allopregnanolone, the primary metabolite of progesterone, induces a rapid and large increase in [Ca2+]i through activation of voltage-gated Ca2+ channels mediated by conversation with GABAA receptors (Dayanithi & Tapia-Arancibia, 1996). In fetal neurones GABA is usually depolarising, whereas in adult neurones GABA is generally hyperpolarising, and this difference in action is associated with maturation of the Cl? gradient (Owens 1996; Ben-Ari 1997; Clayton 1998; Rivera 1999). Interactions between neurosteroids and GABA receptors have drawn particular attention in the case of magnocellular oxytocin neurones. Oxytocin release from your dendrites of supraoptic neurones functions back upon the neurones to reduce the efficacy of GABA, and this effect is blocked by allopregnanolone, leading to the proposal that, at term pregnancy, the fall in progesterone precipitates enhanced.Allopregnanolone, progesterone, 17-oestradiol, gabazine, picrotoxin, bicuculline, muscimol, nicardipine and TTX were obtained from Sigma, France; vasopressin and oxytocin were from Boehringer Mannheim, France; Fura-2 AM and Pluronic F-127 were from Molecular Probes Inc., USA. much smaller, and was enhanced in the presence of bicuculline. The GABAA receptor agonist muscimol also induced oxytocin release from supraoptic nuclei in young rats, but experienced no effect in adult rats. Oxytocin cells isolated from young rats showed an increase in [Ca2+]i in response to both allopregnanolone and muscimol. Allopregnanolone experienced no effect on [Ca2+]i or around the release of oxytocin or vasopressin from neurohypophysial axon terminals in either young or aged rats. We conclude that, in very young rats, (i) neurosteroids induce oxytocin release from your supraoptic nucleus by a mechanism that partly depends on the presence of GABA, which in young rats is usually depolarising to oxytocin cells, and which also partly depends upon endogenous oxytocin, and (ii) the effect of allopregnanolone upon oxytocin release changes with age, as the functional activity of GABAA receptors changes from excitation to SSR240612 inhibition of oxytocin cells. The magnocellular neurones of the hypothalamic supraoptic and paraventricular nuclei project to the neurohypophysis where they release oxytocin or vasopressin into the bloodstream. In addition, oxytocin and vasopressin are released from your cell body and dendrites of these neurones (Ludwig, 1998). This central release occurs semi-independently of release from your axon terminals (Ludwig 2002), and appears to be involved in pre- and post-synaptic regulation of electrical activity (Brussaard 1996; Kombian 1997) via specific receptors whose activation results in an increase in intracellular calcium ([Ca2+]i) (Dayanithi 1996). Central (somato-dendritic) peptide release is also involved in the striking physiologically regulated reorganisation of cellular architecture of the nuclei (Theodosis 1986). The striking morphological plasticity during parturition and lactation is mainly attributable to central oxytocin release (Theodosis 1986), but it is also influenced by steroid hormones (Montagnese 1990). Steroid hormones are potent neuronal modulators that are synthesised by glial cells (Garcia-Segura 1995; Baulieu, 1997) and by some neuronal populations (Sakamoto 2001), as well as deriving from peripheral sources. In addition to their genomic effects, neurosteroids display non-genomic effects in neurones, ranging from modulation of firing rate and neurotransmitter release, induction of sedation, anaesthesia and behavioural changes (Spindler, 1997; Wakerley & Richardson, 1998; McEwen & Alves, 1999; Toran-Allerand 1999; Israel & Poulain, 2000; Leng, 2000). These effects are mediated either by specific SSR240612 receptors or by allosteric modulation of major ligand-gated ion channels such as the GABAA receptor (Twyman & Macdonald, 1992) or the NMDA receptor (Lambert 1995; Rupprecht & Holsboer, 1999; Falkenstein 2000). In 1995, Wang and colleagues demonstrated that oestradiol could induce acute exocytosis of oxytocin and vasopressin from the dendrites of adult hypothalamic neurones, but had no effect on release from neurohypophysial axon terminals (Wang 1995). In fetal rat hypothalamic neurones, allopregnanolone, the primary metabolite of progesterone, induces a rapid and large increase in [Ca2+]i through activation of voltage-gated Ca2+ channels mediated by interaction with GABAA receptors (Dayanithi & Tapia-Arancibia, 1996). In fetal neurones GABA is depolarising, whereas in adult neurones GABA is generally hyperpolarising, and this difference in action is associated with maturation of the Cl? gradient (Owens 1996; Ben-Ari 1997; Clayton 1998; Rivera 1999). Interactions between neurosteroids and GABA receptors have attracted particular attention in the case of magnocellular oxytocin neurones. Oxytocin release from the dendrites of supraoptic neurones acts back upon the neurones to reduce the efficacy of GABA, and this effect is blocked by allopregnanolone, leading to the proposal that, at term pregnancy, the fall in progesterone precipitates enhanced excitability of oxytocin neurones through this effective GABA disinhibition (Brussaard 1999, 2000). Thus the actions of allopregnanolone on GABA effects are complex, and apparently involve protein kinase action (see also Francsik 2000). In the.