Cocaine induces DNA damage in distinct brain areas of female rats under different hormonal conditions

Clin Exp Pharmacol Physiol. 2014 Apr;41(4):265-9. doi: 10.1111/1440-1681.12218.

Abstract

We evaluated levels of neuronal DNA damage after acute or repeated cocaine treatment in different brain areas of female rats after ovariectomy or sham surgery. Rats in the control and acute groups were given saline i.p., whereas in the repeated group were given 15 mg/kg, i.p., cocaine for 8 days. After a 10 day washout period, the control group was given saline i.p., whereas rats in the acute and repeated groups were given a challenge dose of 15 mg/kg, i.p., cocaine. After behavioural assessment, rats were killed and the cerebellum, hippocampus, hypothalamus, prefrontal cortex and striatum were dissected for the Comet assay. Acute cocaine exposure induced DNA damage in all brain areas. This effect persisted after repeated administration, except in the hypothalamus, where repeated treatment did not cause increased DNA damage. Sexual hormones exhibited a neuroprotective effect, decreasing cocaine-induced DNA damage in cycling rats in all brain areas.

Keywords: DNA damage; cocaine; oestrogen; ovariectomy; progesterone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / cytology*
  • Brain / drug effects
  • Cocaine / administration & dosage
  • Cocaine / toxicity*
  • Comet Assay
  • DNA Damage / drug effects*
  • Dopamine Uptake Inhibitors / administration & dosage
  • Dopamine Uptake Inhibitors / toxicity*
  • Estrogens / metabolism*
  • Female
  • Neurons / drug effects*
  • Ovariectomy
  • Rats

Substances

  • Dopamine Uptake Inhibitors
  • Estrogens
  • Cocaine