Specific effect of haloperidol on dopamine turnover in the frontal cortex

Laduron, Pierre M.; Bie, K. De; Leysen, Josée E.

doi:10.1007/bf00508472

Cited by 59 publications

(6 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The neuroleptic-induced elevation of HVA, however, is generally transient, since HYA concentrations generally return to normal or below normal during the course of several weeks of continuous neuroleptic administration Bowers Jr. and Rozitis, 1976;Scatton, 1977Scatton, , 1981aLaduron et al, 1977;Bacopoulos et al, 1979).…”

Section: Neuroleptic Acceleration Ofmentioning

confidence: 99%

Dopamine receptors and the dopamine hypothesis of schizophrenia

Seeman

1987

Synapse

799

383

View full text Add to dashboard Cite

The discovery of neuroleptic drugs in 1952 provided a new strategy for seeking a biological basis of schizophrenia. This entailed a search for a primary site of neuroleptic action. The Parkinsonian effects caused by neuroleptics suggested that dopamine transmission may be disrupted by these drugs. In 1963 it was proposed that neuroleptics blocked "monoamine receptors" or impeded the release of monoamine metabolites. The neuroleptic concentration in plasma water or cerebrospinal fluid was of the order of 2 nM for haloperidol in clinical therapy. A systematic research was made between 1963 and 1974 for a primary site of neuroleptic action which would be sensitive to 2 nM haloperidol and stereoselective for (+)-butaclamol. Direct evidence that neuroleptics selectively blocked dopamine receptors occurred in 1974 with the finding that nanomolar concentrations of these drugs stereoselectively inhibited the binding of [3H]-dopamine or [3H]-haloperidol. These binding sites, now termed D2 dopamine receptors (which inhibit adenylate cyclase), are blocked by neuroleptics in direct relation to the antipsychotic potencies of the neuroleptics. No such correlation exists for D1 receptors (which stimulate adenylate cyclase). Based on the fact that dopamine-mimetic drugs elicited hallucinations, and that neuroleptics caused rigidity, Van Rossum in 1966 had suggested a hypothesis that dopamine pathways may be overactive in schizophrenia. The D2-selective blockade by all neuroleptics (except the monoamine-depleting reserpine) provided strong support for the dopamine hypothesis. Further support now comes from postmortem data and in vivo positron tomographic data, both of which indicate that the density of D2 receptors are elevated in the schizophrenic brain. The postmortem data indicate a bimodal pattern with half the schizophrenics having striatal D2 densities of 14 pmol/g (control is 13 pmol/g) and the other half having 26 pmol/g. Current positron tomographic data indicate D2 densities of 14 pmol/g in control subjects, but values of 34 pmol/g in drug-naive schizophrenics. Future tests of the dopamine hypothesis of schizophrenia may entail an examination of the amino acid composition and genes for D2 receptors in schizophrenic tissue, an examination of the ability of the D2 receptor to become phosphorylated and to desensitize into the low-affinity state, and an examination of the interaction of D2 receptors with D1 receptors or other neurotransmitters.

show abstract

Section: Neuroleptic Acceleration Ofmentioning

confidence: 99%

Dopamine receptors and the dopamine hypothesis of schizophrenia

Seeman

1987

Synapse

799

383

View full text Add to dashboard Cite

show abstract

“…It is there fore very important to define the differences between the PFCx and CPu with respect to the effects of neuroleptics on dopamine (DA) release and metabolism. Numerous studies have been made using experimental animals with single and multiple doses of neurolep tics to evaluate this effect [1][2][3][4][5][6][7][8][9][10], However, contradictory data appear in these reports. Since experimental animals were decapi tated after the injection of neuroleptics and the steady-state levels of acidic metabo lites of DA, 3,4-dihydroxyphenylacetic acid (DOPAC) and/or homovanillic acid (HVA) measured in various brain regions, it seems that the actual dynamics of DA metabolism (DA release into a synaptic cleft) was not reflected in these studies.…”

Section: Introductionmentioning

confidence: 99%

Differential Effect of Haloperidol on Dopamine Release and Metabolism in Caudate Putamen and Anteromedial Frontal Cortex Using Intracerebral Dialysis

Kurata

Shibata

1991

Pharmacology

View full text Add to dashboard Cite

The differential effects of haloperidol on dopamine release and its metabolism were investigated in the anteromedial frontal cortex and the caudate putamen using the intracerebral dialysis method in anesthetized rats after single intraperitoneal injections of 0.01, 0.125 and 2 mg/kg haloperidol. The basal levels of dopamine, 3,4-dihydroxyphenyl-acetic acid and homovanillic acid, collected every 20 min from the caudate putamen, were 22, 7.7 × 103 and 5.5 × 103 pg/30 μl, respectively, and were much higher than those from the anteromedial frontal cortex, which were 1.8, 2.6 × 102 and 4.6 × 102 pg/30 μl, respectively. There was a clear difference in the time-response curve of dopamine release between the two brain regions after the injection of 0.125 mg/kg haloperidol, but no difference after the administration of the other doses. The measurements of 3,4-dihydroxyphenylacetic acid and homovanillic acid showed a difference between the two brain structures after the injection of 0.01 mg/kg haloperidol, but did not show such a clear difference after injection of the other doses. These findings suggest that there is a difference between the anteromedial frontal cortex and the caudate putamen with respect to the regulating mechanism of dopamine release and its metabolism.

show abstract

“…However, the time-response curve of HVA might not be the same for different neuroleptic drugs (Fregnan and Porta 1981), at different doses (Ahtee 1975), and in different brain regions (Fregnan and Porta 1981;Matsumoto et al 1983). Since the question of the maximal effect time of neuroleptics is of some importance to the design and interpretation of laboratory experiments as well as to clinical investigations, we thus carried out a systematic evaluation of the time-response curve of HVA in rat pre-frontal cortex and caudate, which are believed to be important to the antipsychotic actions and the extrapyramidal sideOffprint requests to: W.-H. Chang effects of neuroleptics (Laduron et al 1977;Bacopoulos et al 1979;Matsumoto et al 1983;Chang et al 1986b), following a single dose IP injection of 14 neuroleptics and reduced haloperidol.…”

mentioning

confidence: 99%