Fig. 1
From: The sigma-1 receptor modulates methamphetamine dysregulation of dopamine neurotransmission
σ1R agonist or σ1R overexpression inhibits METH-induced, DAT-mediated increases in the firing rate of dopaminergic neurons. The spontaneous firing activity of mouse midbrain dopaminergic neurons was recorded at resting membrane potential in current clamp mode. Representative traces are shown. a Application of METH (10 μM) significantly increased the spontaneous firing rate frequencies above baseline levels (n = 11 neurons). The firing rate returned to baseline levels following application of the DAT blocker nomifensine (10 μM). b Overexpression of σ1R-EYFP (n = 10 neurons) or c pretreatment with 10 μM of the σ1R agonist PRE-084 (n = 12 neurons) blocked the METH-induced increase in firing rate of dopaminergic neurons. Similar to experiments in (a), application of nomifensine returned the firing rate to baseline levels in σ1R-EYFP expressing and PRE-084-treated neurons. d Representative image of a dopamine neuron expressing σ1R-EYFP immunolabeled for tyrosine hydroxylase (TH) (scale bar: 20 μm). e Representative image of a dopamine neuron expressing GFP-σ1R-siRNA immunolabeled for TH (scale bar: 20 μm). f Western blot shows σ1R levels were decreased after GFP-σ1R-siRNA treatment and unchanged in non-transfected or control siRNA treated cells. g Bar graph shows spontaneous firing rate (spikes per second) in different treatment groups at baseline, after METH treatment, and after subsequent nomifensine treatment. Dopamine neurons treated either with GFP-σ1R-siRNA (n = 10 neurons) or with control siRNA (n = 5 neurons) and neurons derived from σ1R knockout mice (n = 8 neurons) had no change in the METH-induced increase in firing rate compared to control. (F (10,96) = 14.2, P < 0.0001, two-way ANOVA; Sidak’s test for multiple comparisons within baseline, METH, and nomifensine; **** P < 0.001). Data is represented as mean ± SEM
