Attenuated opiate withdrawal reactions inBDNF mutant mice. A–D summarize the observer-based ratings of naloxone-precipitated withdrawal inBDNF conditional mutant mice (black bars) in comparison to littermate wild-type controls (open bars) after chronic morphine administration (500 mg/kg, total dose).A, Total overall withdrawal score; B, total number of checked signs (diarrhea, rhinorhea, lacrimation, ptosis, abnormal posture); C, tremors; D, wet dog shakes; over a 20 min period. Differences between naloxone-treated mutants and controls in A–D are significant (t tests; *p < 0.05, **p < 0.01). E, Acute antinociceptive tolerance in BDNF conditional mutants and controls, measured as maximum possible effect (%MPE) of hot plate latencies 30 min after administration of morphine (10 mg/kg, i.p.) and 24 hr after a one-time challenge with saline or morphine (100 mg/kg). F, Chronic antinociceptive tolerance inBDNF conditional mutants and controls, measured as %MPE in hot plate assay 30 min after administration of morphine (10 mg · kg−1 · d−1) over the course of 5 d. Filled bars, Mutants;open bars, controls. Data are expressed as mean ± SE.