Failure of anticholinergic drugs to antagonize the increase in dopamine seen after gammahydroxybutyric acid and axotomy

Stock, Günter

doi:10.1007/bf01252707

Cited by 4 publications

(1 citation statement)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As a con sequence, the presynaptically located DA autoreceptors [8] are not stimu lated by DA and hence there is a loss of the negative feedback which regu lates DA synthesis following DA release [8] resulting in a dose-dependent increase in the rate of dopa accumulation. Since this increase is not related to postsynaptic events and therefore cannot be blocked by anticholinergic drugs [23] (fig. 3), application of GBL can be used as a model to study sensitivity changes of presynaptically located DA receptors towards endog enously released DA.…”

Section: Discussionmentioning

confidence: 99%

Long-Term Application of Haloperidol: Effects on Dopamine and Acetylcholine Receptors

Stock¹,

Kummer²

1981

Int Pharmacopsychiatry

Self Cite

View full text Add to dashboard Cite

Rats were injected daily with haloperidol, 0.5 mg/kg i.p., or pimozide, 2 mg/kg i.p., for a period of 8 or 16 days, respectively. 24 h after the last injection of haloperidol, these rats were challenged with gamma-butyrolactone (GBL) in doses of 200- 750 mg/kg i.p. In haloperidol-treated rats, higher doses of GBL are needed in order to increase the rate of dopa accumulation. This finding demonstrates the development of supersensitivity of dopamine (DA) autoreceptors towards endogenously released DA. Pimozide had no effect on the increased rate of dopa accumulation induced by increasing doses of GBL. From this data it is concluded that pimozide in our model is mainly active on postsynaptic DA receptors and haloperidol is active on pre- and postsynaptic DA receptors. In rats treated chronically with daily injections of haloperidol, benztropine, in a dose of 50 mg/kg, induced a decrease in dopa accumulation which was more marked than the decrease seen with benztropine, 50 mg/kg in animals treated with a single injection of haloperidol only. The opiate antagonist, naloxone at a dose of 10 mg/kg, had no effect on these results. Benztropine, 50 mg/kg i.p., had no effect on the increased rate of dopa accumulation induced by GBL, 400 mg/kg. The data support the hypothesis that in parallel to the development of supersensitive postsynaptic DA receptors, there is a development of subsensitivity in cholinergic receptors within the nigro-neostriatal system. Further the results show that a new DA-acetylcholine equilibrium is reached during long-term haloperidol treatment. The implications of these findings in regard to extrapyramidal side effects during long-term neuroleptic treatment are briefly discussed.

show abstract

Section: Discussionmentioning

confidence: 99%

Long-Term Application of Haloperidol: Effects on Dopamine and Acetylcholine Receptors

Stock¹,

Kummer²

1981

Int Pharmacopsychiatry

Self Cite

View full text Add to dashboard Cite

show abstract

Anesthetics

Cheng¹

1985

Alterations of Metabolites in the Nervous System

View full text Add to dashboard Cite

Supersensitivity of dopamine-autoreceptors the effect of gammabutyrolactone in long-term haloperidol treated rats

Stock

Steinbrenner

Kummer

1980

J. Neural Transmission

View full text Add to dashboard Cite

Rats were injected daily with haloperidol, 0.5 mg/kg i.p. for a period of 16 days. 24 hours after the last injection of haloperidol these rats were challenged with gammabutyrolactone in doses of 200-750 mg/kg i.p. The ensuing increase in neostriatal dopa-accumulation was significantly lower than in rats not previously treated with haloperidol. Since the increase in dopa-accumulation following GBL-treatment is most probably independent of postsynaptically located DA-receptors the difference between the experimental series is explained in terms of reduced feedback activation of DA-synthesis due to the increased sensitivity of presynaptically located DA-autoreceptors.

show abstract

Failure of anticholinergic drugs to antagonize the increase in dopamine seen after gammahydroxybutyric acid and axotomy

Cited by 4 publications

References 16 publications

Long-Term Application of Haloperidol: Effects on Dopamine and Acetylcholine Receptors

Long-Term Application of Haloperidol: Effects on Dopamine and Acetylcholine Receptors

Anesthetics

Supersensitivity of dopamine-autoreceptors the effect of gammabutyrolactone in long-term haloperidol treated rats

Contact Info

Product

Resources

About