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. 2018 Mar 6;668:7-12.
doi: 10.1016/j.neulet.2017.12.061. Epub 2017 Dec 30.

Effects of BDNF Receptor Antagonist on the Severity of Physical and Psychological Dependence, Morphine-Induced Locomotor Sensitization and the Ventral Tegmental Area-Nucleus Accumbens BDNF Levels in Morphine- Dependent and Withdrawn Rats

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Effects of BDNF Receptor Antagonist on the Severity of Physical and Psychological Dependence, Morphine-Induced Locomotor Sensitization and the Ventral Tegmental Area-Nucleus Accumbens BDNF Levels in Morphine- Dependent and Withdrawn Rats

Masoumeh Khalil-Khalili et al. Neurosci Lett. .

Abstract

This study examined the effects of systemic administration of the TrkB receptor antagonist (ANA-12) on the severity of physical and psychological dependence and morphine-induced locomotor sensitization, the ventral tegmental area (VTA)-nucleus accumbens (NAc) BDNF levels in morphine-dependent and withdrawn rats. Rats were injected with bi-daily doses (10 mg/kg, at 12 h intervals) of morphine for 10 days. Then, rats were tested for naloxone-precipitated morphine withdrawal signs, the anxiety (the elevated plus maze-EPM) after the last morphine injection and injection of ANA12 (ip). Also, morphine-induced locomotor sensitization was evaluated after morphine challenge followed by an injection of ANA-12 in morphine-withdrawn rats. The VTA-NAc BDNF levels were assessed in morphine-dependent and withdrawn rats. The overall Gellert-Holtzman score was significantly higher in morphine-dependent rats receiving ANA-12 than in those receiving saline. Also, the percentage of time spent in the open arms in control and morphine-dependent rats receiving ANA-12 were higher compared to the Cont/Sal and D/Sal rats, respectively. There was no significant difference in the locomotor activity and the VTA-NAc BDNF levels between D/Sal/morphine and D/ANA-12/morphine groups after morphine withdrawal. We conclude that the systemic administration of ANA-12 exacerbates the severity of physical dependence on morphine and partially attenuates the anxiety-like behavior in morphine-dependent rats. However, ANA-12 did not affect morphine-induced locomotor sensitization and the VTA-NAc BDNF levels in morphine-dependent and withdrawn rats.

Keywords: Anxiety; BDNF levels; BDNF receptor antagonist; Locomotor sensitization; Morphine dependence.

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