Withania somnifera prevents morphine withdrawal-induced decrease in spine density in nucleus accumbens shell of rats: a confocal laser scanning microscopy study

Neurotox Res. 2009 Nov;16(4):343-55. doi: 10.1007/s12640-009-9069-2. Epub 2009 Jun 24.


Opiate withdrawal is associated with morphological changes of dopamine neurons in the ventral tegmental area and with reduction of spine density of second-order dendrites of medium size spiny neurons in the nucleus accumbens shell but not core. Withania somnifera has long been used in the Middle East, Africa, and India as a remedy for different conditions and diseases and a growing body of evidence points to its beneficial effects on a number of experimental models of neurological disorders. Recently, many studies focused on the potential neuritic regeneration and synaptic reconstruction properties of its methanolic extract and its constituents (withanolides). This study investigates whether morphine withdrawal-induced spine reduction in the nucleus accumbens is affected by the administration of a Withania somnifera extract. To this end, rats were chronically treated with Withania somnifera extract along with morphine or saline and, upon spontaneous (1 and 3 days) or pharmacologically precipitated withdrawal, their brains were fixed in Golgi-Cox stain for confocal microscopic examination. In a separate group of animals, Withania somnifera extract was administered during three days of spontaneous withdrawal. Withania somnifera extract treatment reduced the severity of the withdrawal syndrome when given during chronic morphine but not during withdrawal. In addition, treatment with Withania somnifera extract during chronic morphine, but not during withdrawal, fully prevented the reduction of spine density in the nucleus accumbens shell in spontaneous and pharmacologically precipitated morphine withdrawal. These results indicate that pretreatment with Withania somnifera extract protects from the structural changes induced by morphine withdrawal potentially providing beneficial effects on the consequences related to this condition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Behavior, Animal / drug effects
  • Chromatography, High Pressure Liquid
  • Dendritic Spines / drug effects*
  • Disease Models, Animal
  • Male
  • Microscopy, Confocal / methods
  • Morphine / blood
  • Morphine / pharmacokinetics
  • Morphine / pharmacology*
  • Morphine Dependence / complications
  • Naltrexone / pharmacology
  • Naltrexone / therapeutic use
  • Narcotic Antagonists / pharmacology
  • Narcotic Antagonists / therapeutic use
  • Neurons / drug effects
  • Neurons / ultrastructure
  • Nucleus Accumbens / cytology*
  • Phytotherapy
  • Plant Extracts / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley
  • Silver Staining / methods
  • Substance Withdrawal Syndrome* / drug therapy
  • Substance Withdrawal Syndrome* / pathology
  • Substance Withdrawal Syndrome* / physiopathology
  • Time Factors
  • Withania / chemistry*


  • Narcotic Antagonists
  • Plant Extracts
  • Naltrexone
  • Morphine