Motivational effects of withdrawal in opiate-dependent animals after blocking BDNF function in the VTA. a, Knocking down TrkB in the VTA with LV-siRNAs did not affect spontaneous opiate somatic withdrawal signs. Both LV-siRNAs (n = 8) and LV-GFP (n = 8) animals show an increase in percentage abstinence scores over time after 16 h heroin administration with respect to saline control animals (n = 8; *p < 0.05). b, Opiate naive (n = 7) and dependent (n = 7) LV-siRNAs-treated animals display a reduction in low-frequency (22 kHz) s compared with opiate naive (n = 7) and dependent (n = 7) LV-GFP-treated animals (*p < 0.05) during naloxone-precipitated chronic opiate withdrawal during the course of a 10 min test session. c, Knocking down TrkB in the VTA with LV-siRNAs blocks the place aversion for 16 h of abstinence from morphine (3 mg/kg) in dependent rats (n = 8). In contrast, control opiate-dependent animals infected with LV-GFP (n = 8) show conditioned place aversions (*p < 0.05). d, Naloxone-conditioned (5 mg/kg) place aversions were blocked in LV-siRNAs-treated (n = 8) dependent animals, but not in LV-GFP-treated (n = 8) animals (*p < 0.05). e, Both LV-siRNAs (n = 8) and LV-GFP (n = 8)-infected animals display a conditioning place aversion to LiCl (5 mg/kg; *p < 0.05). Data represent the means ± SEM the absolute times spent in the previously saline and previously drug paired compartments.