Effects of intermittent and continuous haloperidol administration on the dopaminergic system in the rat brain

Biol Psychiatry. 1986 Jun;21(7):650-6. doi: 10.1016/0006-3223(86)90126-5.


The after-effect of intermittent and of continuous treatment with haloperidol on the dopaminergic system of the rat brain was studied. Each rat was treated for 14 days with either a single daily intraperitoneal injection of haloperidol (intermittent haloperidol group) or with a subcutaneously implanted pump that released haloperidol for 14 days (continuous haloperidol group). The total amount of haloperidol administered was 28 mg/kg in each animal of both groups. On the seventh day after cessation of injections or removal of pumps, the changes in dopamine (DA) metabolism after a challenge dose of haloperidol (1 mg/kg, intraperitoneally) were noted, and the number of [3H]spiperone binding sites in the striatum were recorded. The continuous haloperidol group showed a greater tolerance response to the influence of haloperidol on stimulation of DA turnover and also showed a larger increase in the number of [3H]spiperone binding sites than the intermittent haloperidol group. It is concluded that continuously administered haloperidol exerts a stronger effect on DA transmission, which in turn produces a greater tolerance to an acute dose of haloperidol than intermittent haloperidol administration.

MeSH terms

  • 3,4-Dihydroxyphenylacetic Acid / metabolism
  • Animals
  • Chromatography, High Pressure Liquid
  • Corpus Striatum / drug effects*
  • Corpus Striatum / metabolism
  • Dopamine / metabolism
  • Drug Administration Schedule
  • Haloperidol / pharmacology*
  • Homovanillic Acid / metabolism
  • Male
  • Rats
  • Rats, Inbred Strains
  • Receptors, Dopamine / drug effects*
  • Spiperone / metabolism
  • Synaptic Transmission / drug effects


  • Receptors, Dopamine
  • 3,4-Dihydroxyphenylacetic Acid
  • Spiperone
  • Haloperidol
  • Dopamine
  • Homovanillic Acid