Effects Of Haloperidol Research Articles

A short term prospective study of the effects of the commonly used antipsychotic drugs on ECG parameters

Context: Psychiatric patients have been identified as a population at risk for cardiovascular problems. Mortality rates are higher among psychiatric patients than in the general population and pharmacological treatment may produce side-effects that affect morbidity and mortality. Most of the previous studies are cross-sectional and are done without taking the base line values and they do not mention clearly the effects of antipsychotic drugs when used for a short period. Aims: To compare the effects of Olanzapine (OLZ), Risperidone (RSP), Trifluperazine (TFP) and Haloperidol (HPL) antipsychotic drugs on various ECG Parameters. Settings and Design: Short term prospective study. Materials and Methods: All the consecutive patients attending the hospital, who mandated the use of antipsychotic drugs, were recruited. A baseline electrocardiogram (ECG) was recorded on Day 0, before starting the antipsychotic drug. ECGs were repeated on Days 1, 5 and 10 after starting the drug. A total of 71 patients were included (N = 71), of which 33 were in OLZ group (N = 33), 14 in the RSP group (N = 14), 13 in the TFP group (N = 13) and 11 in HPL group (N = 11). Statistical analysis used: The data was analysed using SPSS Ver. 14 software. Results: No statistically significant differences were found in the ECG parameters in patients on OLZ, RSP, TFP and HPL. Conclusions: Our study shows that there are no significant changes in ECG parameters after administration of OLZ, RSP, TFP and HPL. Thus all the four drugs are equally safe in healthy adults for short-term use.

<i>Vitamin</i> D<sub>3</sub> Receptor Activation Rescued Corticostriatal Neural Activity and Improved Motor-Cognitive Function in -D<sub>2</sub>R Parkinsonian Mice Model

Background: fourth generation antipsychotics have been implicated in the blockade of calcium signalling through inhibition of dopamine receptive sites on dopaminergic D2 Receptor (D3R). As a result of the abnormal calcium signalling associated with D2R inhibition, changes occur in the motor and memory neural axis leading to the observed behavioural deficits after prolonged haloperidol. Thus, Vitamin D3 receptor (VD3R), a calcium controlling receptor in the striatum can be targeted to relief the neurological symptoms associated with haloperidol (-D2R) induced PD. Aim: This study sets to investigate the role of VD3R activation in vitro and in vivo after haloperidol-induced Dopaminergic (D2R) blockade. In addition, we examined the associated neural activity and behavioural changes in parkinsonian and VDRA intervention mice. Methods: Dopaminergic D2R inhibition was investigated in vitro using Melanocytes isolated from the scale of a Tilapia. In four separate set ups, the cells were cultured in calcium free Ringer’s solution as follows; 300 μM haloperidol, 100 μM VD3, 100 mM calcium chloride and a combination of 300 μM haloperidol and 100 μM VD3. Subsequently, dopaminergic vesicle accumulation and calcium signalling were observed in bright field microscopy using blue and green fluorescence probes. In the second phase, PD was induced in adult BALB/c mice (-D2; n = 8) after 14 days of intraperitoneal haloperidol treatment (10 mg/Kg). A set of n = 4 mice were untreated (-D2) while the other group (n = 4) received 100 mg/Kg of VD3 for 7 days (-D2/+VDR). The control groups (n = 4 each) were treated with normal saline (NS) and VD3 (+VDR) for 14 days. At the end of the treatment phase, the animals were assessed in Rotarod, parallel bar-, cylinder-, Y-Maze-, one trial place recognition- and novel object recognition-(NOR) tests. Neural activity was measured using chronic electrode implants placed in the M1 (motor cortex), CPu (striatum), CA1 (hippocampus) and PFC (prefrontal cortex). Neural activity was compared with the outcomes of behavioural tests for memory and motor functions and data was expressed as mean ± SEM (analysed using ANOVA with Tukey post-hoc test, significant level was set at 0.05). Results/Discussion: in vitro outcomes show that VDR increase calcium signalling and reverses the effect of haloperidol; specifically by reducing dopaminergic vesicle accumulation in the cell body. Similarly, in vivo neural recordings suggest an increase in calcium hyperpolarization currents in the CPu and PFC of intervention mice (-D2/+VDR) when compared with the parkinsonian mice (-D2). These animals (-D2/+VDR) also recorded an improvement in spatial working memory and motor function versus the Parkinsonian mice (-D2). These outcomes suggest the role of CPu-PFC corticostriatal outputs in the motor-cognitive decline seen in parkinsonian mice. Similarly, VDRA reduced the neural deficits through restoration of calcium currents (burst activities) in the intervention mice (-D2/+VDR). Conclusion: VDRA treatment reduced the motor-cognitive defects observed in haloperidol induced PD. Our findings suggest the role of VDRA in restoration of calcium currents associated with PFC and CPu corticostriatal outputs seen as burst frequencies in in vivo neural recording.

Leukopenia in a patient on haloperidol decanoate: a case report

We are reporting a case of leukopenia developed in a patient on haloperidol decanoate injections. A literature review revealed it as an uncommon side effect of antipsychotics; however, regular monitoring of blood cell count is crucial in patients on antipsychotics. In this case report, we discussed the effective doses, side effects, and drug interactions of haloperidol decanoate. Neuroleptic malignant syndrome is a rare but serious side effect of haloperidol.

Clozapine promotes glycolysis and myelin lipid synthesis in cultured oligodendrocytes.

Clozapine displays stronger systemic metabolic side effects than haloperidol and it has been hypothesized that therapeutic antipsychotic and adverse metabolic effects of these drugs are related. Considering that cerebral disconnectivity through oligodendrocyte dysfunction has been implicated in schizophrenia, it is important to determine the effect of these drugs on oligodendrocyte energy metabolism and myelin lipid production. Effects of clozapine and haloperidol on glucose and myelin lipid metabolism were evaluated and compared in cultured OLN-93 oligodendrocytes. First, glycolytic activity was assessed by measurement of extra- and intracellular glucose and lactate levels. Next, the expression of glucose (GLUT) and monocarboxylate (MCT) transporters was determined after 6 and 24 h. And finally mitochondrial respiration, acetyl-CoA carboxylase, free fatty acids, and expression of the myelin lipid galactocerebroside were analyzed. Both drugs altered oligodendrocyte glucose metabolism, but in opposite directions. Clozapine improved the glucose uptake, production and release of lactate, without altering GLUT and MCT. In contrast, haloperidol led to higher extracellular levels of glucose and lower levels of lactate, suggesting reduced glycolysis. Antipsychotics did not alter significantly the number of functionally intact mitochondria, but clozapine enhanced the efficacy of oxidative phosphorylation and expression of galactocerebroside. Our findings support the superior impact of clozapine on white matter integrity in schizophrenia as previously observed, suggesting that this drug improves the energy supply and myelin lipid synthesis in oligodendrocytes. Characterizing the underlying signal transduction pathways may pave the way for novel oligodendrocyte-directed schizophrenia therapies.

Differential effects of clozapine, metoclopramide, haloperidol and risperidone on acquisition and performance of operant responding in rats.

Prior research has not systematically investigated the effects of systemic antipsychotic drugs on operant response acquisition, specifically their behavioural microstructure, reinforcement blunting and relative potency in acquisition compared to performance once operant responding has stabilized. This study aims to systematically investigate the effects of systemically administered clozapine, metoclopramide, haloperidol and risperidone during free operant response acquisition and performance. Following magazine training, food-restricted male Wistar rats lever pressed for food reward in 15 min daily operant conditioning sessions. All drugs suppressed operant response acquisition and performance. Risperidone and metoclopramide, but not clozapine or haloperidol, suppressed operant responding more potently during acquisition than performance. The dopamine D2-like receptor antagonists haloperidol and metoclopramide that affect the ventral and dorsal striatum blunted reinforcement and decreased inactive lever presses in acquisition. In contrast, the atypical antipsychotics clozapine and risperidone that affect the ventral striatum and prefrontal cortex failed to decrease inactive lever presses during acquisition, suggesting a possible decision-making deficit. Haloperidol decreased active lever pressing over performance days. The drugs did not appear to affect rats' sensitivity to active lever press outcome, even though they suppressed active lever pressing. Results suggest that reinforcement impact during operant acquisition is dependent on dopamine D2 receptors while drugs affecting, among other areas, the prefrontal cortex produce a deficit in ability to suppress inactive lever press responses.

Feasibility of prophylactic haloperidol to prevent delirium in cancer patients.

232 Background: Approximately 2.5 million cancer patients are hospitalized annually and 25-40% of them will suffer from delirium; yet the majority of delirium is not diagnosed or treated. Delirium rates vary by age and reason for hospitalization and can be as high as 70% in hematopoietic stem cell transplant (HSCT) patients post-transplantation. Delirium can have devastating short and long-term complications and research is ongoing to see if it can be prevented. This study aims to: 1) demonstrate the feasibility of using prophylactic haloperidol in HSCT patients; 2) determine the side effects of oral haloperidol in HSCT patients; and 3) explore the hypothesis that prophylactic haloperidol will reduce the rate of delirium following HCST. Methods: All cognitively intact HSCT patients at a large academic institution were approached for study inclusion. Patients with delirium at time of screening or antipsychotic use in the previous 30 days were excluded. All participants received 5 mg oral haloperidol the night prior to transplant and nightly for 2 weeks post-transplant. Participants were seen daily to evaluate for side effects and every other day to evaluate for delirium using the Delirium Rating Scale (DRS-98). Results: Of the 19 patients who enrolled: 5 withdrew; 9 completed the full (2 week) study; and 5 completed a portion of the study. 22% (2 of 9) patients developed delirium (compared to a historical rate of 43% on our unit). Haloperidol was well tolerated with no evidence of major side effects (1 report of mild restlessness and 1 patient had transient evidence of sedation). Conclusions: Oral haloperidol was well tolerated in HSCT patients. While this study was not designed to detect differences in delirium incidence it provides promising evidence that prophylactic haloperidol may decrease delirium post-HSCT.

Neuroprotective effect of ziprasidone: Preliminary results compared to haloperidol

Typical and atypical antipsychotic drugs are widely used to treat psychosis. The resent study investigated whether ziprasidone, an atypical antipsychotic drug, has a neuroprotective effect on hippocampal neurons in rats with experimentallyinduced transient cerebral ischemia comparatively with haloperidol which is a typical antipsychotic. Transient cerebral ischemia was induced by 10-minute occlusion of bilateral carotis communis arteries. The rats were divided into four groups: Shamoperated control group (Group I), ischemia control group (Group II), haloperidol-treated group (Group III) and ziprasidone-treated group (Group IV). Following 10-minute ischemia, Group III received 1mg/kg haloperidol intramuscularly and Group IV received 2.5 mg/kg ziprasidone intraperitoneally. The animals were sacrificed on the seventh day following induced ischemia to determine the number of intact neurons at hippocampus and dentate gyrus to demonstrate the effects of ischemia and efficacy of the treatments administered. Surviving cell numbers were found in the sham operated group; 198, in the ischemia control group; 80, in the haloperidol-treated group; 185, in ziprasidonetreated group; 189. The groups showed significant difference in the comparison of the surviving cell numbers. However, the number of surviving cells did not significantly different between the ziprasidone and haloperidol-treated group. Previous studies with the ischemia model have demonstrated protective effects of haloperidol on hippocampal region. The findings of the present study show that ziprasidone, which is an atypical antipsychotic drug, may produce neuroprotective effects as potent as haloperidol, which is a typical antipsychotic drug.

Neuroprotective effect of ziprasidone: Preliminary results compared to haloperidol

Typical and atypical antipsychotic drugs are widely used to treat psychosis. The resent study investigated whether ziprasidone, an atypical antipsychotic drug, has a neuroprotective effect on hippocampal neurons in rats with experimentallyinduced transient cerebral ischemia comparatively with haloperidol which is a typical antipsychotic. Transient cerebral ischemia was induced by 10-minute occlusion of bilateral carotis communis arteries. The rats were divided into four groups: Shamoperated control group (Group I), ischemia control group (Group II), haloperidol-treated group (Group III) and ziprasidone-treated group (Group IV). Following 10-minute ischemia, Group III received 1mg/kg haloperidol intramuscularly and Group IV received 2.5 mg/kg ziprasidone intraperitoneally. The animals were sacrificed on the seventh day following induced ischemia to determine the number of intact neurons at hippocampus and dentate gyrus to demonstrate the effects of ischemia and efficacy of the treatments administered. Surviving cell numbers were found in the sham operated group; 198, in the ischemia control group; 80, in the haloperidol-treated group; 185, in ziprasidonetreated group; 189. The groups showed significant difference in the comparison of the surviving cell numbers. However, the number of surviving cells did not significantly different between the ziprasidone and haloperidol-treated group. Previous studies with the ischemia model have demonstrated protective effects of haloperidol on hippocampal region. The findings of the present study show that ziprasidone, which is an atypical antipsychotic drug, may produce neuroprotective effects as potent as haloperidol, which is a typical antipsychotic drug.

Effects of haloperidol on Kv4.3 potassium channels

Haloperidol is commonly used in clinical practice to treat acute and chronic psychosis, but it also has been associated with adverse cardiovascular events. We investigated the effects of haloperidol on Kv4.3 currents stably expressed in CHO cells using a whole-cell patch-clamp technique. Haloperidol did not significantly inhibit the peak amplitude of Kv4.3, but accelerated the decay rate of inactivation of Kv4.3 in a concentration-dependent manner. Thus, the effects of haloperidol on Kv4.3 were estimated from the integral of the Kv4.3 currents during the depolarization pulse. The Kv4.3 was decreased by haloperidol in a concentration-dependent manner with an IC50 value of 3.6μM. Haloperidol accelerated the decay rate of Kv4.3 inactivation and activation kinetics in a concentration-dependent manner, thereby decreasing the time-to-peak. Haloperidol shifted the voltage dependence of the steady-state activation and inactivation of Kv4.3 in a hyperpolarizing direction. Haloperidol also caused an acceleration of the closed-state inactivation of Kv4.3. Haloperidol produced a use-dependent block of Kv4.3, which was accompanied by a slowing of recovery from the inactivation of Kv4.3. These results suggest that haloperidol blocks Kv4.3 by both interacting with the open state of Kv4.3 channels during depolarization and accelerating the closed-state inactivation at subthreshold membrane potentials.

Antidepressant and antipsychotic drugs differentially affect PON1 enzyme activity

Human serum paraoxonase (PON1, EC 3.1.8.1.) is a high-density lipid (HDL)-associated, calcium-dependent enzyme. In this study, the effects of Haloperidol, Fluoxetine hydrochloride, Diazepam and Acepromazine drugs used for the therapy of antidepressant and antipsychotic diseases, on paraoxonase enzyme activity was studied in in vitro inhibition studies on purified human serum PON1. PON1 enzyme was purified from human blood using two-step procedures, namely, ammonium sulfate precipitation and sepharose-4B-l-tyrosine-1-napthylamine hydrophobic interaction chromatography. The overall purification of human serum PON1 was obtained in a activity of 109.29 U/mL and this enzyme was purified 125-fold. The SDS–polyacrylamide gel electrophoresis of the enzyme indicates a single band with an apparent MW of 43 kDa. Inhibition studies indicated that haloperidol and fluoxetine hydrocloride were effective inhibitors on purified human serum PON1 activity with IC50 of 0.187 and 3.08 mM values, respectively. The kinetics of interaction of haloperidol and fluoxetine hydrocloride with the purified human serum PON1 indicated uncompetitive inhibiton pattern with Ki of 4.15 and 0.007 mM, respectively.

Different effects of Bifeprunox, Aripiprazole, and Haloperidol on body weight gain, food and water intake, and locomotor activity in rats

Following on the success of Aripiprazole with its high clinical efficacy and minimal side effects, further antipsychotic drugs (such as Bifeprunox) have been developed based on the same dopamine D2 partial agonist pharmacological profile as Aripiprazole. However clinical trials of Bifeprunox have found differing results to that of its predecessor, without the same significant clinical efficacy. This study has therefore investigated the different effects of 10week treatment with Aripiprazole (0.75mg/kg, 3 times per day), Bifeprunox (0.8mg/kg, 3 times per day) and Haloperidol (0.1mg/kg, 3 times per day) on body weight gain, food and water intake, white fat mass, and 8week treatment on locomotor activity. Treatment with Bifeprunox was found to significantly reduce all of the measured parameters except white fat mass compared to the control group. However, Aripiprazole and Haloperidol treatment reduced water intake compared to the control, without any significant effects on the other measured parameters. These findings further demonstrate the potential pharmacological differences between Aripiprazole and Bifeprunox, and identify potential weight loss side effects and increased anxiety behaviour with Bifeprunox treatment.

Anticipatory and foraging behaviors in response to palatable food reward in chickens: Effects of dopamine D2 receptor blockade and domestication

Behaviors associated with anticipation and search for palatable food may provide information about dopaminergic reward processes and positive motivational affect in animals. The overall aim was to investigate the involvement of dopamine signaling in the regulation of cue-induced anticipation and search for palatable food reward in chicken, and whether domestication has affected expression of reward-related behaviors. The specific aims were to describe effects of mealworms (palatable food for hens) and haloperidol (a dopamine D2 antagonist) on foraging behaviors and cue-induced anticipatory behaviors in Red Junglefowl (RJF; the wild ancestor of modern laying hens) and a white layer hybrid (LSL). RJF (n=26) and LSL (n=20) were initially trained on a conditioning schedule to anticipate mealworms (unconditioned stimulus; US) 25s after exposure to a red light (conditioned stimulus; CS). For the experiment, hens received haloperidol or saline injections 30min before exposure to one CS+US combination. Behavior was registered 10min before CS and 10min after US (foraging behaviors), and during the CS–US interval (anticipatory behaviors). Higher frequencies of CS-induced anticipatory head movements, faster approach to rewards, and higher frequency of foraging behaviors were found in LSL compared to RJF. Haloperidol suppressed CS-induced head movements in both breeds, and the frequency of foraging behaviors after reward delivery. The results support a role of dopamine signaling in the regulation of reward processes in chickens, and suggest that domestication has changed the threshold for perceiving food incentives and/or for expressing reward-related behaviors that may be indicative of positive motivational affect in hens.

Chronic haloperidol increases voltage-gated Na+ currents in mouse cortical neurons

Typical antipsychotics are characterized by extrapyramidal syndrome (EPS). Previous studies demonstrated that typical antipsychotics could inhibit neuronal voltage-gated sodium channel (VGSC). However, EPS typically emerge only upon prolonged exposure. As a result, we examined effects of haloperidol, a prototype typical antipsychotic, on neuronal VGSC upon incubation for varying duration. Briefly, VGSC currents were activated and recorded using a whole-cell patch-clamp technique in primary culture of mouse cortical neurons. VGSC activity was inhibited by acute haloperidol exposure (for minutes), but enhanced in a time- and concentration-dependent manner by chronic haloperidol exposure (for hours). The effects of chronic haloperidol were associated with increased expression of VGSC subunits as well as corresponding electrophysiological channel properties. In summary, we found enhanced VGSC currents upon chronic haloperidol exposure in cortical neurons in contrast to inhibition by acute haloperidol exposure. Such a results may contribute to EPS of typical antipsychotics.

Repeated but not acute treatment with ∆9-tetrahydrocannabinol disrupts prepulse inhibition of the acoustic startle: Reversal by the dopamine D2/3 receptor antagonist haloperidol

Cannabis produces cognitive dysfunctions that resemble those of schizophrenia; yet the neurobiological substrate of this similarity remains unclear. Schizophrenia patients show deficits in prepulse inhibition (PPI) of the acoustic startle reflex (ASR), an operational measure of the information-processing abnormalities that may underlie the cognitive and positive symptoms of the disease. However, the effect of cannabis on PPI remains poorly understood, as data are often contradictory. Here, we investigated the effect of acute and repeated treatment with ∆9-tetrahydrocannabinol (THC), the main psychoactive constituent of cannabis, on PPI in rats, and the role of dopamine D2/3-receptor blockade in this effect. PPI and ASR were sequentially measured after the first and the last dose of a 21-days treatment with THC (1mg/kg/day) or vehicle and at 1-week following discontinuation of treatment. The effect of haloperidol (0.1mg/kg) on THC-induced PPI alteration was also evaluated. Chronic, but not acute, THC treatment produced significant reductions in PPI that were normalized back to control values within one-week of THC discontinuation. The THC-induced gating deficits were observed in the absence of ASR change and were reversed by the D2/3-receptor antagonist haloperidol. Chronic THC exposure induced PPI disruptions that emerged only following repeated administrations, suggesting that time-dependent neuroadaptations within the DA mesolimbic system are involved in the disruptive effects of THC on sensorimotor gating. These gating deficits were transient and appeared to be dependent on an overactivity of D2/3-receptor-mediated dopamine signaling, highlighting a potential role for D2/3-receptors in the propsychotic action of THC.

Effect of Intravenous Haloperidol on the Duration of Delirium and Coma in Critically Ill Patients (Hope-ICU)

In critically ill patients the administration of regular haloperidol did not reduce the incidence of delirium or coma. Level of evidence: 1B (single-centre randomised controlled trial with low risk of bias)

Poster #S18 ADVANCED PATERNAL AGE AS A RISK FACTOR FOR SCHIZOPHRENIA: A TRANSLATIONAL STUDY IN HUMANS AND RATS

Compounds possessing 5-HT1A agonist properties attenuate catalepsy induced by D2 receptor blockade. Here we examined the role of 5-HT1A receptor agonism in the reduced cataleptogenic potential of several novel antipsychotic agents in the crossed leg position (CLP) and the bar catalepsy tests in rats. When administered alone, ziprasidone produced marked catalepsy, whereas aripiprazole, bifeprunox, SLV313, SSR181507 and sarizotan did not. However, when 5-HT1A receptors were blocked with the selective antagonist, WAY100635 (0.63 mg/kg, SC), robust cataleptogenic properties of SLV313, bifeprunox and sarizotan were unmasked and the catalepsy induced by ziprasidone was accentuated. In contrast, only modest catalepsy was induced by aripiprazole and SSR181507, even following a higher dose of WAY100635 (2.5 mg/kg). This suggests that these compounds possess other anti-cataleptic properties, such as partial agonism at dopamine D2 receptors. The capacity to reverse neuroleptic-induced catalepsy was investigated in interaction studies with haloperidol (2.5 mg/kg, SC). Whereas ziprasidone and aripiprazole did not markedly reduce the effects of haloperidol, SLV313 and sarizotan attenuated CLP catalepsy. In contrast, SSR181507 and bifeprunox potently inhibited both CLP and bar catalepsy. Taken together, these data show that 5-HT1A receptor activation reduces the cataleptogenic potential of novel antipsychotic agents but indicate marked diversity in the contribution of 5-HT1A and/or other mechanisms to the profiles of the drugs.

Combination Effect of Methadone and Haloperidol on Morphine Withdrawal-Induced Anxiety in Male Mice

Combination Effect of Methadone and Haloperidol on Morphine Withdrawal-Induced Anxiety in Male Mice

Effects of dopaminergic modulation on automatic semantic priming: a double-blind study

Enhanced automatic spreading of activation in the semantic network has been suggested to underlie formal thought disorder in patients with schizophrenia, but it is not clear how this relates to the dopaminergic dysfunction implicated in the disorder. Previous studies on dopaminergic modulation of priming in healthy volunteers have focused on controlled rather than automatic processes. The present study aimed to examine the effects of both a dopaminergic agonist and a dopaminergic antagonist on semantic priming while minimizing the contribution of controlled processes. We investigated the effects of levodopa (L-Dopa; 100 mg), haloperidol (2 mg) and placebo on priming in healthy participants within a randomized, double-blind, crossover design. We used a pronunciation priming task with word triplets; the middle word was an ambiguous word, whereas the first word of the triplet served to provide either a congruent, incongruent or unbiased context for the target word. Two stimulus onset asynchronies (SOA) were used: 150 ms and 750 ms. The study involved 34 participants. At an SOA of 150 ms, L-Dopa accelerated responses to incongruent targets and subordinate targets of ambiguous words, whereas haloperidol was associated with faster responses in congruent contexts and dominant targets. At an SOA of 750 ms, haloperidol accelerated responses to subordinate targets. Modulations in the relative magnitude of priming according to substance and condition rather than absolute priming were assessed. Effects of L-Dopa on automatic priming processes appear to be different than those on controlled processes. Our results are consistent with those of studies on semantic priming and the effects on antipsychotics in patients with schizophrenia.

Effects of Short-Term Administration of Haloperidol on the Background of Impairments to Brain Metabolism and Neuron Activity

The effects of amphetamine and haloperidol on spike activity levels, the ability to acquire a conditioned defensive reflex to time, and the state of components of the dopaminergic system in neurons in the sensorimotor cortex and caudate nucleus in rabbits were studied. Chronic administration of amphetamine increased the level of neuron spike activity and the ability to acquire and reproduce conditioned reflexes in the sensorimotor cortex, and decreased these parameters in the caudate nucleus. Biochemical studies demonstrated hyperactivation of the dopaminergic system in the caudate nucleus, as compared with the sensorimotor cortex. On the background of chronic amphetamine, haloperidol induced effects in both locations which were close to those of single doses to intact animals. The neuroleptic led to suppression of neuron activity and a decrease in the number of conditioned reactive neurons in the sensorimotor cortex, in contrast to neurons in the caudate nucleus. Short-term exposure to haloperidol produced changes in biochemical parameters towards normalization of neurotransmitter metabolism.

In vivo Effect of Apomorphine and Haloperidol on MPP+ Neurotoxicity

The involvement of dopaminergic (DAergic) receptor drugs in the neuroprotection against the neurotoxic action of 1-methyl-4-phenylpyridinium (MPP⁺) in the DAergic terminals in striatum was studied using an intracerebral microdialysis technique. Twenty-four hours after surgery (day 1), apomorphine and haloperidol, alone or with 1 mmol/l of MPP⁺ perfusion through the microdialysis probe, were systemically administered. Forty-eight hours after surgery (day 2), 1 mmol/l of MPP⁺ was perfused for 15 min in all groups of animals and the output of dopamine was measured. The amount of dopamine was directly proportional to the remaining striatal DAergic terminals. The results show that: (1) subcutaneous administration of apomorphine before MPP⁺ perfusion prevented MPP⁺-induced neurotoxicity, and (2) intraperitoneal administration of haloperidol before MPP⁺ perfusion did not prevent MPP⁺-induced neurotoxicity.