Figure 4.

Hsp90 inhibition increases opioid-induced withdrawal symptoms. Acute (A) and chronic (B) morphine dependence and withdrawal paradigms were established with concurrent vehicle and 17-AAG (0.5 nmol) i.c.v. injections as described under “Experimental procedures.” Withdrawal was precipitated with 10 mg/kg (acute) or 30 mg/kg (chronic) naloxone i.p. with behaviors recorded for 20 min. Jumps and urine/feces weight are reported for each paradigm as the mean ± S.D. *, p < 0.05 versus the same measure vehicle control by unpaired two-tailed t test; n = 24–29 mice/group for each paradigm; three technical replicates were used for each paradigm by the same experimenter using different mouse cohorts on different days. 17-AAG treatment increased urine and feces weight, but not jumps, in both paradigms. C, mice were exposed to three 3-min training sessions on a Rotarod device followed by vehicle or 0.5 nmol of 17-AAG injected i.c.v. and a 24-h recovery. Another 3-min trial was then performed with acceleration from 4 to 16 rpm and no further treatment. The sample size reported for individual mice consisted of one technical replicate. 17-AAG had no effect on Rotarod performance (p > 0.05). Data are reported as the mean ± S.D.