Haloperidol-induced Changes Research Articles

The effect of ethanol and haloperidol on dopamine receptor (D2) density

The study was performed to investigate the influence of ethanol on haloperidol-induced changes of the dopamine (D 2) receptors in rat striatal membrane preparations. Subchronic administration of the neuroleptic in the drinking water resulted in an increase of the number of binding sites in a dose-dependent manner. Simultaneous treatment with both haloperidol and ethanol prevented the rise of D 2 receptors.

Lithium prevents adaptation of brain dopamine systems to haloperidol in schizophrenic patients

To evaluate the effect of lithium treatment on haloperidol-induced changes of brain dopamine systems, cerebrospinal fluid homovanillic acid (HVA) was assessed in nine patients during a sequential treatment protocol with placebo, lithium, lithium plus acute haloperidol, and lithium plus chronic haloperidol. None of the patients developed tolerance to the rise in HVA during treatment with haloperidol and lithium. Concurrent treatment with lithium appears to prevent the development of tolerance in dopamine metabolism during chronic haloperidol treatment. These data provide the first evidence in man that lithium may prevent neuroleptic-induced functional supersensitivity of brain dopamine systems.

Haloperidol-induced changes in blink rates correlate with changes in BPRS score.

Spontaneous eye blink rates, psychiatric symptoms and response to neuroleptic medication may all be mediated by dopamine. Fixed doses of haloperidol, a dopamine blocking agent, were administered for six weeks to 17 chronic schizophrenic patients who had been previously withdrawn from all medications. The change in blink rates caused by haloperidol corresponded to a change in the thought disturbance syndrome which measures positive symptoms (r = .48, P less than .05). The relationship was particularly clear in patients with normal cerebral ventricles (r = .74, P less than .01).

Response of striatonigral substance P systems to a dopamine receptor agonist and antagonist

Striatonigral substance P pathways have been postulated to be the excitatory component of a feedback loop which assists in modulating the activity of the nigrostriatal dopaminergic system. Data presented in this paper supports this hypothesis by demonstrating that alterations in dopamine receptor activity resulted in significant changes in the Striatonigral substance P system as measured by nigral levels of substance P-like immunoreactivity. Thus, both activation and blockade of dopamine receptors by apomorphine and haloperidol, respectively, resulted in specific, dose-dependent and reversible decreases in the concentration of nigral substance P-like immunoreactivity. The mechanisms mediating apomorphine- and haloperidol-induced changes in nigral substance P levels appear to be different because of the dissimilar time-response pattern and an antagonism of the apomorphine effect by haloperidol. These results suggest that dopamine receptor activity, mediated by the nigrostriatal dopaminergic system, exerts significant influence on the substance P Striatonigral feedback loop.

Effects of intranigral administration of dopamine agonists and antagonists and baclofen on concentrations of dopac and dopamine in the striatum and substantia nigra of the rat.

Systemic administration of haloperidol to rats failed to alter the concentration of dopamine but increased the concentration of 3,4-dihydroxy-phenylacetic acid (DOPAC), the major metabolite of dopamine, in both the striatum and substantia nigra. These haloperidol-induced changes in DOPAC were prevented by an intranigral microinjection of baclofen, a drug which reduces nigrostriatal dopaminergic neuronal activity. It has been proposed that nigrostriatal neurons are regulated, in part, by the activation of autoreceptors in substantia nigra. However, intranigral microinjections of high concentrations of several dopaminergic antagonists failed to mimic the biochemical effects resulting from systemic administration of these drugs; instead, they slightly increased the concentrations of both dopamine and DOPAC in the striatum and decreased dopamine in substantia nigra. Intranigral microinjections of the dopamine agonist, apomorphine, failed to alter the concentration of DOPAC in the striatum, but reduced both dopamine and DOPAC in the nigra. If DOPAC concentrations reflect nigrostriatal dopaminergic neuronal activity, the present results suggest that dopaminergic agonists and antagonists acting in substantia nigra do not exert a major influence on the activity of these neurons.

Effects of para-chlorophenylalanine on amphetamine and haloperidol-induced changes in striatal dopamine turnover

Para-chlorophenylalanine (PCPA) was administered to rats, and the animals were sacrificed 48 h later. Animals received various doses of S(+)-amphetamine (AMPH) 31 min before sacrifice or of haloperidol (HAL) 46 min before sacrifcie and an intracerebral injection of [ 3H]tyrosine 15 min prior to sacrifice. PCPA pretreatment potentiated the increased accumulation of striatal [ 3H]dopamine (DA) induced by doses of AMPH to 1.5 mg/kg, and inhibited the decrease in striatal [ 3H]DA accumulation observed at higher doses (> 2.5 mg/kg) of AMPH. Furtherm the AMPH-induced increase in endogeneous levels of striatal DA was inhibited by PCPA pretreatment. Similarily, PCPA pretreatment potentiated the HAL-induced increase in striatal [ 3H]DA accumulation. The data are discussed with respect to an inhibitory serotonergic influence on nigrostriatal DA function, and the relationship of nigrostriatal biochemical events to AMPH-induced behavioral changes.

Testing of a hypothesis for osmotic opening of the blood-brain barrier.

Testing of a hypothesis for osmotic opening of the blood-brain barrier.