Altered Acoustic Startle Reflex, Prepulse Inhibition, and Peripheral Brain-Derived Neurotrophic Factor in Morphine Self-Administered Rats

Int J Neuropsychopharmacol. 2017 May 1;20(5):383-391. doi: 10.1093/ijnp/pyw107.


Background: Previous studies suggested that opiate withdrawal may increase anxiety and disrupt brain-derived neurotrophic factor function, but the effects of i.v. morphine self-administration on these measures remain unclear.

Methods: Adult male Sprague-Dawley rats were implanted with a catheter in the jugular vein. After 1 week of recovery, the animals were allowed to self-administer either i.v. morphine (0.5 mg/kg per infusion, 4 h/d) or saline in the operant conditioning chambers. The acoustic startle reflex and prepulse inhibition were measured at a baseline and on self-administration days 1, 3, 5, and 7 (1- and 3-hour withdrawal). Blood samples were collected on self-administration days 3, 5, and 7 from separate cohorts of animals, and the levels of brain-derived neurotrophic factor and corticosterone were assayed using the enzyme-linked immunosorbent assay method.

Results: Compared with the saline group, the morphine self-administration group showed hyper-locomotor activity and reduced defecation during the self-administration. The morphine self-administration increased acoustic startle reflex at 1-hour but not 3-hour withdrawal from morphine and disrupted prepulse inhibition at 3-hour but not 1-hour withdrawal. The blood brain-derived neurotrophic factor levels were decreased in the morphine self-administration group at self-administration days 3 and 5, while the corticosterone levels remained unchanged throughout the study.

Conclusions: The current findings suggest that spontaneous withdrawal from i.v. morphine self-administration may have transient effects on acoustic startle, sensorimotor gating, and peripheral brain-derived neurotrophic factor levels, and these changes may contribute to the adverse effects of opiate withdrawal.

Keywords: acoustic startle reflex; brain-derived neurotrophic factor; corticosterone; i.v. morphine self-administration; opiate withdrawal; prepulse inhibition.

MeSH terms

  • Acoustic Stimulation
  • Analgesics, Opioid / administration & dosage
  • Analgesics, Opioid / pharmacology*
  • Analysis of Variance
  • Animals
  • Brain-Derived Neurotrophic Factor / blood*
  • Conditioning, Operant / drug effects
  • Enzyme-Linked Immunosorbent Assay
  • Hydrocortisone / blood
  • Male
  • Morphine / administration & dosage
  • Morphine / pharmacology*
  • Prepulse Inhibition / drug effects*
  • Rats
  • Rats, Sprague-Dawley
  • Reflex, Startle / drug effects*
  • Self Administration
  • Time Factors


  • Analgesics, Opioid
  • Brain-Derived Neurotrophic Factor
  • Morphine
  • Hydrocortisone