The central nervous system (CNS) is able to synthesize and/or metabolize steroid hormones. These neuroactive steroids are capable of modulating several brain functions and, among these, they seem to regulate the hypothalamic-pituitary-gonadal (HPG) axis. Indeed, recent observations have shown that 5 alpha-pregnane-3 alpha-ol-20-one (allopregnanolone), one of the most abundant naturally occurrin...

Among neurosteroids, allopregnanolone is the most potent endogenous positive modulator of GABA(A) receptors, and disturbances in its release may play a role in pathomechanism of some neurological and psychiatric disorders. In contrast to a large body of evidence on allopregnanolone involvement in pathogenesis of epilepsy, no data are available on its role in pseudoseizures. Therefore, the aim o...

This study examines the early effects of 3 alpha-hydroxy-5 alpha-pregnan-20-one (allopregnanolone on cytosolic free calcium concentration ([Ca2+]i in primary cultures of fetal rat hypothalamic neurons. Microspectrofluorimetry of fluorescent Ca2+(-)sensitive indicator Fura-2 was used to quantify these changes. Allopregnanolone (1 pM to 100 nM) increased [Ca2+]i within 2-3 sec, in a dose dependen...

There is a growing amount of evidence for a neuroprotective role of progesterone and its neuroactive metabolite, allopregnanolone, in animal models of neurodegenerative diseases. By using a model of hemiparkinsonism in male rats, injection of the neurotoxic 6-OHDA in left striatum, we studied progesterone's effects on rotational behavior induced by amphetamine or apomorphine. Also, in order to ...

Alterations in GABA(A) receptor expression have been associated with the allopregnanolone (3α-hydroxy-5α-pregnan-20-one; 3α,5α-THP) antidepressant-like effect in rats. The present study aimed to verify the effect of bilateral, intra-nucleus accumbens core (intra-AcbC) administration of the neurosteroid allopregnanolone on behaviors in the forced swim and grooming microstructure tests and in the...

The effects of the neurosteroid 3alpha-hydroxy-5alpha-pregnane-20-one (allopregnanolone) on synaptic and GABA-evoked currents in acutely dissociated neurons from the medial preoptic nucleus of rat were investigated by perforated-patch recordings under voltage-clamp conditions. The effect of 2.0 microM allopregnanolone on GABA-evoked currents depended strongly on the GABA concentration: the curr...

The inhibitory neurotransmitter !-aminobutyric acid (GABA) has multiple receptors. In mammals, the GABAA receptor subtype is modulated by neurosteroids. However, whether steroid interaction with the GABAA receptor is unique to mammals or a conserved feature in vertebrates is unknown. Thus, neurosteroid modulation of the GABAA receptor was investigated in the brain of the bullfrog (Rana catesbei...

Restorative/protective therapies to restore dopamine neurons in the substantia nigra pars compacta (SNpc) are greatly needed to effectively change the debilitating course of Parkinson's disease. In this study, we tested the therapeutic potential of a neurogenic neurosteroid, allopregnanolone, in the restoration of the components of the nigrostriatal pathway in MPTP-lesioned mice by measuring st...

Ethanol consumption during pregnancy may induce profound changes in fetal CNS development. We postulate that some of the effects of ethanol on striatal glutamatergic transmission and neurotrophin expression could be modulated by allopregnanolone, a neurosteroid modulator of GABAA receptor activity. We describe the acute pharmacological effect of allopregnanolone (65 μg/kg, s.c.) administered to...

The objective of this study was to characterize the impact of allopregnanolone, a neurosteroid that acts as a positive allosteric modulator of synaptic and extrasynaptic GABAA receptors, on interictal spikes and high-frequency oscillations (ripples: 80-200 Hz, fast ripples: 250-500 Hz) in the pilocarpine model of mesial temporal lobe epilepsy. Seven out of 25 Sprague-Dawley rats experiencing 1 ...