Fig 4. Behavioral Analysis of Rat Locomotor Activity.

Graphs illustrate average total locomotor activity (ambulatory, fine, and rearing movements) ± SEM. (A) Chronic morphine administration (10 mg/kg sc twice-daily for 6.5 days; n = 11) was associated with locomotor sensitization when measured on day 7. It was significantly different (F(3,30) = 26.05, p<0.001) in comparison to saline control (n = 9; p<0.001), acute morphine group (saline sc twice-daily for 6 days and morphine 10 mg/kg sc in the morning on day 7; n = 9; p<0.001), and chronic mecamylamine (Mec) administration (2 mg/kg sc twice-daily for 6.5 days; n = 5; p<0.001). Panel B illustrates acute Mec effect on expression of locomotor activation (F(3,30) = 15.21, p<0.001). Mec was administered in a single dose on day 7 (0.5 or 2 mg/kg dose) to animals that were chronically treated with morphine. Although 0.5 mg/kg acute Mec dose (n = 7) statistically decreased locomotor sensitization associated with chronic morphine administration (p = 0.036), it was the 2 mg/kg dose (n = 7; p<0.001) that decreased it to the saline control level. Panel C illustrates chronic Mec effect on development of locomotor sensitization (F(3,30) = 12.37, P<0.001). Mec was administered twice daily in 0.5 or 2 mg/kg dose along morphine for 6 days. Prior to the locomotor testing in the morning of day 7, animals received only morphine. Smaller Mec dose (n = 7) had no effect, while 2 mg/kg chronic Mec administration (n = 7) significantly decreased development of locomotor sensitization in comparison to the chronic morphine group (p>0.006). However, it was still significantly higher in comparison to saline control (p<0.02). Data for saline control and chronic morphine group is the same in A–C. One-way ANOVA with LSD post-hoc test; *, statistically different from all other groups; #, statistical difference only between marked groups.