Fig. 5

σ₁R activation decreases acute METH-mediated behavioral responses. After 30-min habituation to the locomotor chamber, C57BL/6 mice were pretreated with either saline, 1–8 mg/kg PRE-084, or 10 or 30 mg/kg BD1063 by i.p. injection followed by treatment with (a) 2 mg/kg METH or (b) saline after 15 min. Locomotor activity was detected via automated locomotor chambers during the habituation, pretreatment, and 60 min after saline or METH treatment at 5 min bins. c Graph shows the total locomotor activity after the second injection (METH or saline). Whereas METH alone increased locomotion, 8 mg/kg PRE-084 and 30 mg/kg BD-1063 both decreased METH-stimulation of locomotion, while all other doses tested had no effect on baseline or METH-stimulated locomotion. (n = 8 mice for METH treatment, 6 mice for saline treatment, F _(6,86) = 3.418, P = 0.0045 two-way ANOVA, Sidak’s multiple comparisons within saline or METH, ***P = 0.0007 and ****P < 0.0001). d Locomotor activity measured during the 15 min after pretreatment but prior to METH treatment in experiments performed in Fig. 5a and b revealed 30 mg/kg BD1063 acutely decreased locomotor activity in the rodents. (n = 8 mice for all groups, F _(6,93) = 3.356, P = 0.0049, one-way ANOVA; Dunnett’s test for multiple comparisons against saline, **P = 0.0095). e C57BL/6 mice were pretreated with either saline or 10 or 30 mg/kg BD1063 by i.p. injection followed by treatment with saline or 8 mg/kg PRE-084 after 15 min. Mice then received a third injection of either saline or 2 mg/kg METH after 15 min and locomotor activity was measured for 60 min. f While 10 mg/kg BD1063 modestly blocked of the effect of PRE-084 on reducing METH-stimulated locomotor activity over time, treatment with 30 mg/kg BD1063, similar to Fig. 5a and c, resulted in a significant decrease in METH-induced locomotor activity (F _(4,35) = 4.247, P = 0.0002, one-way ANOVA; Tukey’s test for multiple comparisons, ***P = 0.001, *P < 0.02, **P = 0.0034). Data is represented as mean ± SEM