+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Opposite effects of low versus high dose haloperidol treatments on spontaneous and apomorphine induced motor behavior: evidence that at a very low dose haloperidol acts as an indirect dopamine agonist



Opposite effects of low versus high dose haloperidol treatments on spontaneous and apomorphine induced motor behavior: evidence that at a very low dose haloperidol acts as an indirect dopamine agonist



Behavioural Brain Research 229(1): 153-159



Anti-psychotic drugs are antagonists at the dopamine D2 receptors and repeated administration can lead to the development of dopamine receptor supersensitivity. In two experiments, separate groups of rats were administered 1 daily low or high doses of the typical anti-psychotic drug haloperidol (.3 or 1. mg/kg). The high dose decreased locomotion whereas, the low dose increased locomotion. After five days of withdrawal, all groups received 2. mg/kg apomorphine on 5 successive days. The apomorphine treatments given to the vehicle group generated a progressive locomotion sensitization effect and this effect was potentiated by pre-exposure to .3 mg/kg haloperidol. Initially, the prior high dose of haloperidol exaggerated the apomorphine locomotor stimulant effect but with repeated apomorphine treatments desensitization developed. Following a five day withdrawal period an apomorphine challenge test was conducted and apomorphine sensitization was absent in the haloperidol high dose pre-exposure group but potentiated in the low dose pre-exposure group. In the second replication experiment a conditioning test instead of a sensitization challenge test was conducted five days after completion of the five day apomorphine treatment protocol. The repeated apomorphine treatments induced conditioned hyper- locomotion and this conditioned effect was prevented by the prior high dose haloperidol pre-exposure but enhanced by the prior low dose haloperidol pre-exposure. Two new key findings are (a) that a low dose haloperidol regimen can function as a dopamine agonist and these effects persist after withdrawal and (b) that repeated apomorphine treatments can desensitize D2 receptors previously sensitized by a high dose haloperidol treatment regimen.Chronic high dose haloperidol (HAL) treatment induced receptor DA supersensitivity. The high dose supersensitivity did not account for apomorphine (APO) sensitization. Chronic low dose did not induce supersensitivity but potentiated sensitization. Chronic low dose haloperidol regimen can function as a dopamine agonist. Repeated APO desensitizes D2 receptors previous sensitized by a high dose of HAL..

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 054761152

Download citation: RISBibTeXText

PMID: 22244923

DOI: 10.1016/j.bbr.2011.12.042


Related references

The effect of serotonergic agents on haloperidol-induced striatal dopamine release in vivo: Opposite role of 5-HT2A and 5-HT2C receptor subtypes and significance of the haloperidol dose used. Neuropharmacology 39(6): 1053-1063, April 3, 2000

Apomorphine and haloperidol-induced effects on male rat sexual behavior: no evidence for actions due to stimulation of central dopamine autoreceptors. Pharmacology, Biochemistry, and Behavior 21(3): 463-466, 1984

Haloperidol-induced plasma prolactin release: sensitivity, reliability, and comparison to haloperidol antagonism of dopamine agonist-induced stereotyped behavior in the rat. Psychopharmacology 78(4): 383-384, 1982

Opposite effects of typical and atypical anti-psychotic drugs on sensitized dopamine receptors: sub-chronic low dose Olanzapine exposure reverses sensitization but a similar regimen of low dose haloperidol potentiates sensitization effects. Psychopharmacology 230(4): 579-588, 2014

Effects of treatments with apomorphine, haloperidol and ethanol on apomorphine-induced changes in body temperature in the rat. Neuropharmacology 23(9): 1109-1112, 1984

Haloperidol serum concentrations and D2 dopamine receptor occupancy during low-dose treatment with haloperidol decanoate. International Clinical Psychopharmacology 12(5): 255-262, 1997

Haloperidol serum concentrations and D2 dopamine receptor occupancy during low-dose treatment with haloperidol decanoate. International Clinical Psychopharmacology 12(5): 255-261, 1998

Actigraphic measurement of the effects of single-dose haloperidol and olanzapine on spontaneous motor activity in normal subjects. Journal of Psychiatry & Neuroscience 28(4): 293-299, 2003

Disposition of Haloperidol and Reduced Haloperidol Plasma Levels After Single Dose Haloperidol Decanoate Administration. Human Psychopharmacology. 10(1): 47-51, 1995

Haloperidol and reduced haloperidol plasma concentrations after a loading dose regimen with haloperidol decanoate. Progress In Neuro-Psychopharmacology & Biological Psychiatry. 20(1): 73-86, 1996

Behavioral supersensitivity to apomorphine and amphetamine after chronic high dose haloperidol treatment. Psychopharmacology Communications 1(3): 285-293, 1975

Neurochemical and motor effects of high dose haloperidol treatment: exacerbation by tryptophan supplementation. Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine 200(4): 571-575, 1992

Effects of apomorphine and haloperidol on spontaneous stereotyped licking behavior in the cebus monkey. Psychopharmacology 85(2): 240-243, 1985

Benefit and risk of high-dose metoclopramide in comparison to high-dose haloperidol or triflupromazine in cisplatin-induced vomiting. Klinische Wochenschrift 63(9): 428-432, 1985

The opposite effect of a low and a high dose of serotonin-1A agonist on behavior induced by MK-801. Neuropharmacology 52(4): 1071-1078, 2007