Steroids ModulateN-Methyl-D-aspartate-Stimulated [³H]Dopamine Release from Rat Striatum via σ Receptors

Abstract

Steroids have been proposed as endogenous ligands at receptors. In the current study, we examined the ability of steroids to regulate N-methyl-D-aspartate (NMDA)-stimulated [ 3 H]dopamine release from slices of rat striatal tissue. We found that both progesterone and pregnenolone inhibit [ ,7,8,9,10, (LY379196) against both progesterone and pregnenolone. We found that LY379196 at 30 nM reversed the inhibition of release by both progesterone and pregnenolone. These findings support steroids as candidates for endogenous ligands at receptors.

Modifications of Neuroactive Steroid Levels in an Experimental Model of Nigrostriatal Degeneration: Potential Relevance to the Pathophysiology of Parkinson’s Disease

“…Relatively high levels of PROG, and its derivatives, DHP and THP, have been previously detected in the human SNc and caudate nucleus, with respect to other brain areas (Bixo et al 1997), suggesting that substantial synthesis and accumulation of neuroactive steroids may take place in the nigrostriatal system. Various studies have also reported that neuroactive steroids can affect synaptic transmission at the cortico-striatal level, by modulating the striatal release of dopamine (Nuwayhid and Werling 2003;Sadri-Vakili et al 2008;Whittaker et al 2008). Moreover, neuroactive steroids can act as either positive or negative modulators of the GABA-A receptor (Belelli and Lambert 2005); this class of molecules may, therefore, intervene in the modulation of basal ganglia circuitry activity, where GABAergic transmission plays a crucial role at various sites (Blandini et al 2000).…”

Steroid pregnenolone sulfate enhances NMDA‐receptor‐independent long‐term potentiation at hippocampal CA1 synapses: Role for L‐type calcium channels and sigma‐receptors

“…Neurosteroid interactions at sigma-receptors have been reported to either positively or negatively modulate NMDARmediated responses in CNS (Hayashi et al, 1995;Monnet et al, 1995;Debonnel et al, 1996a,b;Nuwayhid and Werling, 2003;Bermack and Debonnel, 2005). Therefore, it was important to determine that blockade of sigma-receptors by BD1047 did not modulate NMDAR-dependent LTP induced by 100 Hz stimulation at CA1 synapses.…”

Dextromethorphan as a Potential Neuroprotective Agent With Unique Mechanisms of Action

“…[93][94][95][96] Sigma receptors regulate the release of neurotransmitters, 6,97 and are thought to do so by modulating calcium influx and intracellular calcium mobilization, and by acting upon PKC pathways. 6,95 It is hypothesized that selective sigma ligands mediate neuroprotection by indirectly inhibiting ischemicinduced presynaptic glutamate release. 10 The reduction of glutamate release by DM 9 may therefore relate to a sigmarelated inhibition of VGCC-dependent synaptic release.…”