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locomotor sensitization and the ventral tegmental area-nucleus accumbens BDNF levels in morphine- dependent and withdrawn rats

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

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locomotor sensitization, the ventral tegmental area (VTA)-nucleus accumbens (NAc) BDNF levels in morphine-dependent and withdrawn rats.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locomotor sensitization was evaluated after morphine challenge followed by an injection of ANA-12 in morphine-withdrawn rats. The VTA-NAc BDNF levels were assessed in morphine-dependent and withdrawn rats.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ANA-12 did not affect morphine-induced locomotor sensitization and the VTA-NAc BDNF levels in morphine-dependent and withdrawn rats.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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anxiety / drug therapy*
  • Azepines / administration & dosage
  • Azepines / pharmacology*
  • Behavior, Animal / drug effects
  • Benzamides / administration & dosage
  • Benzamides / pharmacology*
  • Brain-Derived Neurotrophic Factor / drug effects
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Male
  • Maze Learning / drug effects*
  • Morphine Dependence / drug therapy*
  • Motor Activity / drug effects*
  • Nucleus Accumbens* / drug effects
  • Nucleus Accumbens* / metabolism
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / pharmacology*
  • Rats
  • Rats, Wistar
  • Receptor, trkB / antagonists & inhibitors*
  • Severity of Illness Index
  • Substance Withdrawal Syndrome / drug therapy*
  • Ventral Tegmental Area* / drug effects
  • Ventral Tegmental Area* / metabolism

Substances

  • ANA 12 compound
  • Azepines
  • Benzamides
  • Brain-Derived Neurotrophic Factor
  • Protein Kinase Inhibitors
  • Receptor, trkB