Effects of intermittent and continuous haloperidol administration on the dopaminergic system in the rat brain.
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.
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D004334:Drug Administration Schedule; D006220:Haloperidol / Q000494:pharmacology*; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D013134:Spiperone / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects
D011954:Receptors, Dopamine; D015102:3,4-Dihydroxyphenylacetic Acid; D013134:Spiperone; D006220:Haloperidol; D004298:Dopamine; D006719:Homovanillic Acid