Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “HALOPERIDOL”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 379 records · Page 21Linked to original sources
PubMed2003

Effects of clozapine, olanzapine and haloperidol on the microstructure of ingestive behaviour in the rat.

RATIONALE: Antipsychotic drugs, particularly the newer atypical compounds, have been associated with rapid weight gain in a clinical setting. However, there are few reported animal models producing reliable hyperphagia correlating with the human weight gain liability of these drugs. OBJECTIVE: To compare the effects of the classic neuroleptic haloperidol with the atypical antipsychotics clozapine and olanzapine on the microstructure of ingestive behaviour in rats. METHODS: Male hooded Lister rats drank a palatable high-calorie fat emulsion (10% Intralipid) during 30-min test sessions and microstructural analyses were made following administration of each drug over a range of doses. RESULTS: Clozapine (0.3 mg/kg) and olanzapine (0.1, 0.3, 1 mg/kg) significantly increased intake, whilst haloperidol (0.05, 0.1, 0.2 mg/kg) significantly decreased drinking. No significant changes in the latency to the first lick were observed following any of the drugs tested. Median interlick intervals showed small, dose-related increases after clozapine (3.0 mg/kg), olanzapine (0.3, 1.0 mg/kg) and haloperidol (0.1, 0.2 mg/kg). Olanzapine (1.0 mg/kg) significantly elevated the number of clusters of licking (bouts of licking separated by pauses greater than 500 ms), whilst clozapine and haloperidol did not. Mean cluster size (licks per cluster) was not affected by clozapine or olanzapine, but haloperidol (0.025, 0.05, 0.1, 0.2 mg/kg) produced marked, significant decreases in cluster size. CONCLUSIONS: Clozapine and olanzapine increased fat intake whereas haloperidol did not, and this resembles the greater weight gain liability of atypical antipsychotics in humans. A delay or reduction of the post-ingestive satiety signal combined with preserved palatability appears to be the mechanism responsible for fat hyperphagia in rats treated with clozapine and olanzapine. Conversely, haloperidol leaves satiety unaffected but reduces the palatability of the fat emulsion resulting in reduced intake.

Animals↗
PubMed2005

ACP-103, a 5-HT2A/2C inverse agonist, potentiates haloperidol-induced dopamine release in rat medial prefrontal cortex and nucleus accumbens.

RATIONALE: Atypical antipsychotic drugs (APDs) such as clozapine, olanzapine, quetiapine, risperidone, and ziprasidone are serotonin (5-HT)(2A) antagonists and relatively weaker dopamine (DA) D(2) antagonists, with variable 5-HT(2C) antagonist properties. The ability of atypical APDs to preferentially increase DA release in the cortex compared to the limbic system is believed to be due in part to their antagonism of 5-HT(2A) and D(2) receptors and believed to contribute to their beneficial effects on cognition, negative, and psychotic symptoms. Previous studies from this laboratory using microdialysis have shown that pretreatment of the 5-HT(2A) antagonist M100907 with the typical APD and D(2) antagonist haloperidol produced an increase in the medial prefrontal cortex (mPFC), but not in the nucleus accumbens (NAC), DA release. However, pretreatment with the 5-HT(2A/2C) receptor antagonist SR46349-B with haloperidol increased both mPFC and NAC DA release, suggesting that both 5-HT(2A) and 5-HT(2C) properties may be important for atypical APD effects. OBJECTIVE: The purpose of this study was to examine the effects of a novel putative atypical APD ACP-103 on mPFC and NAC DA release using in vivo microdialysis in freely moving rats that are awake. ACP-103 is an inverse agonist at both 5-HT(2A) and 5-HT(2C) receptors and has intermediate affinities for 5-HT(2C) receptors relative to their affinities for 5-HT(2A) receptors compared to M100907 and SR46349-B. In addition, the effects of ACP-103 were compared to M100907 and SR46349-B, and ACP-103 was also coadministered with haloperidol. RESULTS: ACP-103 10.0 mg/kg, but not 3.0 mg/kg, increased DA release in the mPFC, while neither dose increased DA release in the NAC. Like M100907, ACP-103 (3.0 mg/kg) potentiated 0.1 mg/kg haloperidol-induced DA release in the mPFC while inhibiting that in the NAC. However, ACP-103 (3.0 mg/kg), similar to SR46349-B, potentiated a high dose of haloperidol (1.0 mg/kg)-induced DA release in both regions. The potent 5-HT(2C) antagonist SB242084 1.0 mg/kg significantly potentiated 0.1 mg/kg haloperidol-induced DA release in both the mPFC and NAC. However, SB242084, at 0.2 mg/kg, significantly potentiated DA release only in the NAC. Moreover, SB242084 0.2 mg/kg potentiated DA release in the NAC produced by the combination treatment of 3 mg/kg ACP-103 and 0.1 mg/kg haloperidol. CONCLUSION: These data suggest that the relative extent of 5-HT(2A) and 5-HT(2C) antagonism, as well as the extent of D(2) receptor blockade, has a critical influence on DA release in the mPFC and NAC and may be a determining factor in the action of this class of atypical APDs on these two potentially clinically relevant parameters.

Aminopyridines↗
PubMed1996

Long-term haloperidol administration enhances and short-term administration attenuates the behavioral effects of cocaine in a place conditioning procedure.

Many behavioral effects of cocaine are attenuated by dopamine (DA) receptor antagonists. Yet, long-term DA antagonist administration enhances neuronal responsiveness to DA in several pathways, including the mesolimbic system. This study compared the effects of short-term versus long-term administration of the DA antagonist, haloperidol, on cocaine place conditioning. In the short-term study, rats were maintained on haloperidol or vehicle for the 10 days of place conditioning. Place conditioning to moderate doses of cocaine (10-15 mg/kg) was attenuated significantly, consistent with the dopaminergic actions of haloperidol and cocaine. In the second study, rats were administered haloperidol after place conditioning which had no effect on the expression of this behavior. Finally, rats were maintained on haloperidol for 30 days prior to and throughout place conditioning and testing which resulted in significant place conditioning at low cocaine doses (2.5-7.5 mg/kg). Because these cocaine doses do not support place conditioning in vehicle-maintained rats, these data suggest that long-term haloperidol administration enhances the sensitivity to these behavioral effects in contrast to the attenuation seen with short-term haloperidol administration. These results have wide-ranging implications for cocaine abuse treatment, particularly among schizophrenic populations.

Analysis of Variance↗
PubMed1997

Improvement of acute exacerbations of schizophrenia with amisulpride: a comparison with haloperidol. PROD-ASLP Study Group.

Amisulpride is a substituted benzamide with high selectivity for dopaminergic D2 and D3 receptors. This study compared 800 mg/day amisulpride and 20 mg/day haloperidol in patients with acute exacerbations of schizophrenia. This multicenter, double-blind trial involved 191 patients allocated, after a 1 to 7-day wash-out period, to amisulpride (n = 95) or haloperidol (n = 96) for 6 weeks. Improvement of mean BPRS total score was 48% for amisulpride and 38% for haloperidol (NS), whereas improvement in the Negative PANSS subscale was greater in the amisulpride group (37%) compared to haloperidol (24%) (P = 0.038). CGI scores showed a higher number of responders in the amisulpride (62%) than in the haloperidol group (44%) (P = 0.014). More extrapyramidal symptoms measured with the Simpson-Angus scale were provoked in the haloperidol group (P = 0.0009). Amisulpride is at least as effective as haloperidol in the treatment of acute exacerbations of schizophrenia, and is more effective in the treatment of negative symptoms whilst causing less parkinsonism.

Adult↗
PubMed1998

Chronic haloperidol produces a time- and dose-related slowing of lick rhythm in rats: implications for rodent models of tardive dyskinesia and neuroleptic-induced parkinsonism.

In order to characterize the development of orolingual motor effects of chronic haloperidol treatment in rats, this typical neuroleptic was administered for 102 days while daily measurements of tongue movement dynamics (peak force, lick rhythm, number of licks) during water licking were recorded. After chronic haloperidol dosing (vehicle, 0.06. 0.12, 0.24 mg/kg for four separate groups) for 32 days and continuing every second or third day of the chronic dosing period, the effects of cholinergic (scopolamine: 0.05-0.20 mg/kg; trihexyphenidyl: 0.15-1.0 mg/kg) or serotonergic (ritanserin: 0.5-4.0 mg/kg; quipazine: 0.5-4.0 mg/kg) probe drugs were examined for their capacity to antagonize the alterations in licking behavior induced by haloperidol. Haloperidol dose-dependently reduced peak force and number of licks, effects which were apparent within 2 or 3 days of the start of treatment. Significant effects of haloperidol on lick rhythm first emerged on day 13 and gradually increased in magnitude through the remaining treatment period. Scopolamine, trihexyphenidyl, and quipazine reduced haloperidol's effects on at least one measure of licking behavior. During a 7-day haloperidol withdrawal period, the four dosage groups were similar on all measures of tongue dynamics. Overall, the results exhibited features suggesting the co-occurrence of Parkinson-like and tardive dyskinesia-like effects.

Animals↗
PubMed1998

Haloperidol-induced extrapyramidal reaction: lack of protective effect by vitamin E.

Haloperidol treatment has been shown to produce oxidative stress in patients with acute psychosis. Oxidative stress has also been implicated in the extrapyramidal symptoms (EPS) produced by haloperidol. Supporting the oxidative stress hypothesis, vitamin E (antioxidant) has demonstrated therapeutic efficacy in idiopathic parkinsonism. The prophylactic efficacy of vitamin E (antioxidant) on haloperidol-induced EPS was examined in a randomized controlled trial. The sample consisted of 24 acute psychotic patients hospitalized for a 2-week trial. All patients received oral haloperidol 10 mg/day. The sample was equally randomized to receive either haloperidol alone or haloperidol + vitamin E (3200 IU/day). EPS was rated at recruitment, both live and with video records, and on days 3, 7, 10 and 14. Psychopathology was rated at recruitment and weekly thereafter. Vitamin E had no prophylactic effect on drug-induced EPS, though it did not interfere with the therapeutic efficacy of haloperidol.

Adolescent↗
PubMed1988

Haloperidol alters rat CNS cholinergic system: enzymatic and morphological analyses.

Chemical and morphological changes in cholinergic marker enzymes, acetylcholinesterase (AChE), and choline acetyltransferase (ChAT) of striatum, hippocampus, and cerebral cortex were studied following haloperidol treatment of rats. After short-term (7-21 days) haloperidol treatment, the levels of both enzymes (AChE and ChAT) were increased in striatum and hippocampus (greater than 25%), but not in cortex. After long-term (+40 days) haloperidol treatment, the level of AChE activity returned to control levels in all brain areas, whereas the levels of striatal and hippocampal ChAT decreased by 26% and 29%, respectively. No change in levels of both enzymes was detected after acute treatment (single dose) of haloperidol or chronic treatment with either clozapine or imipramine. Morphological analysis of cholinergic neurons and their processes using monoclonal antibody to ChAT showed two types of changes following 40 days of haloperidol treatment. First, parallel to the observed decrease in the levels of ChAT activity there was a visual decrease in the immunoreactivity in neurons as well as in their processes in striatum and hippocampus. Second, there was an apparent reduction in the size and number of stained neurons and their processes. No changes were seen in immunoreactivity after an acute treatment with haloperidol. These results indicate that the chronic haloperidol treatment in rats causes changes in central cholinergic systems that may be relevant to the pathophysiology of schizophrenia and its treatment.

Acetylcholinesterase↗
PubMed1995

Monosialoganglioside cotreatment prevents haloperidol treatment-associated loss of cholinergic enzymes in rat brain.

Effects of monosialoganglioside (GM1 ganglioside) cotreatment with haloperidol (HAL) were studied in rat on the haloperidol treatment-associated changes in cholinergic enzymes, choline acetyltransferase (ChAT), and acetylcholinesterase (AChE) in three brain regions of interest: striatum, hippocampus, and cerebral cortex. Short-term (8 days) haloperidol treatment significantly increased the levels of both ChAT and AChE in all the three regions of brain, as compared with controls (for ChAT: p < .0001 for all comparisons, and for AChE: striatum: p < .0001; hippocampus: p < .0003; cortex: p < .05). Cotreatment with GM1 ganglioside further increased the ChAT activity relative to haloperidol treatment alone in all three regions (p < .05). The AChE activity was also significantly higher than controls in all three regions (p < .05 for all comparisons) and higher than haloperidol treatment only in hippocampus (p < .02). After chronic haloperidol treatment (45 days), ChAT activity in cortex had returned to control values in both HAL and HAL + GM1 groups, with no significant group differences remaining (p = .10). By contrast, relative to control values, HAL and HAL + GM1 groups both showed lower ChAT activity in the striatum, as well as in the hippocampus (p < .0001 for both), with significantly lower ChAT activity in the HAL than in the HAL + GM1 group for both areas (p = < .0001 for both). AChE activity showed a significant difference only between the HAL and HAL + GM1 groups in the cortex (p = .003), but no significant effects of group were seen on AChE activity in either striatum or hippocampus. These data suggest that the protective effects of GM1 ganglioside cotreatment on haloperidol-induced alterations in cholinergic systems can be relevant for protecting against the complications of neuroleptic-induced parkinsonism.

Animals↗
PubMed1991

Regulation of sigma receptors and responsiveness to guanine nucleotides following repeated exposure of rats to haloperidol: further evidence for multiple sigma binding sites.

The sigma binding sites are postulated to be involved in various central nervous system (CNS) disorders. The neuroleptic drug, haloperidol, displays high affinity for these receptor sites in the CNS. In the present study the effect of repeated exposure of rats to haloperidol (4 mg/kg/day for 14 days) on sigma binding sites labeled with (+)-3-(3-hydroxyphenyl)-N-1-(propyl)piperidine [+)-3-PPP) and 1,3-di-o-tolyl-guanidine (DTG) was investigated. In addition, the regulatory effect of guanine nucleotides on the binding of these two ligands to brain membranes derived from saline and haloperidol-treated rats was examined. Repeated administration of haloperidol induced down-regulation of (+)[3H]-3-PPP binding sites (75% decrease in the number of binding sites compared to control) which persisted for at least 7 days after termination of the haloperidol-treatment. The down-regulation of (+)-3-PPP binding sites was accompanied by reduced responsiveness to guanine nucleotides (i.e. 5-guanylylimidodiphosphate (Gpp(NH)p) compared to the sensitivity of (+)-3-PPP binding sites to the nucleotides tested in control membranes. However, at the 28th day after termination of the haloperidol-treatment, a complete recovery in the total number of (+)[3H]-3-PPP binding sites was observed, and the sensitivity to guanine nucleotides was regained. These findings suggest a marked plasticity in (+)-3-PPP/sigma receptor binding activity. In contrast, [3H]DTG binding sites expressed neither sensitivity to the repeated exposure to haloperidol nor to guanine nucleotides, suggesting a distinction between DTG and (+)-3-PPP binding sites in rat brain.

Adenosine Triphosphate↗
PubMed1994

Uridine potentiates haloperidol's disruption of conditioned avoidance responding.

The pyrimidine nucleoside, uridine, has been proposed as a potential supplement in the treatment of psychosis based on its ability to reduce haloperidol-induced dopamine release. These experiments investigated the effect of uridine (32 mg/kg, i.p.) coadministered with the neuroleptic haloperidol, on rats engaged in one way conditioned avoidance responding. Uridine itself had no effect on animals' performance, while haloperidol (dose range 0.05-0.4 mg/kg, i.p., 90 min before test session) decreased number of avoidances and increased avoidance and escape latencies in a dose-dependent manner. When coadministered with haloperidol, uridine significantly potentiated the disruption of avoidance and avoidance latency induced by haloperidol. This potentiation was still evident after chronic (27 days) uridine treatment. Importantly, coadministration of uridine did not potentiate haloperidol-induced increase of escape latency. The potentiation of haloperidol-induced disruption of conditioned avoidance responding suggests that uridine coadministration might enhance the antipsychotic action of traditional neuroleptics. This would allow for a reduction in the therapeutic dose of the antipsychotic, thereby reducing side effect frequency.

Animals↗
PubMed1994

Haloperidol-induced morphological changes in striatum are associated with glutamate synapses.

Sub-chronic treatment with the typical neuroleptic, haloperidol (0.5 mg/kg/d, s.c.), but not the atypical neuroleptic, clozapine (35 mg/kg/day, s.c.), causes an increase in synapses containing a perforated postsynaptic density (referred to as 'perforated' synapses) and in dopamine (DA) D2 receptors within the caudate nucleus [46]. To determine if these perforated synapses are glutamatergic, we systemically co-administered MK-801 (0.3 mg/kg/day for 2 weeks), a non-competitive antagonist at the N-methyl-D-aspartate (NMDA) receptor-associated ion channel, and haloperidol. MK-801 blocked the haloperidol-induced increase in striatal perforated synapses, but not the haloperidol-induced increase in DA D2 receptors. Injection of MK-801 into the striatum also attenuated the haloperidol-induced increase in perforated synapses. Post-embedding immuno-gold electron microscopy using antibodies to glutamate indicated that the gold particles were localized within striatal presynaptic nerve terminals that make contact with perforated postsynaptic densities. These findings support the hypothesis that the haloperidol-induced increase in perforated synapses is regulated by the NMDA subtype of excitatory glutamate receptor. The increase in perforated synapses following administration of haloperidol, which is associated with a high incidence of extrapyramidal side effects (EPS), and the lack of a synaptic change following administration of clozapine, known to have a low frequency of EPS, suggests that glutamate synapses play a role in the motoric side effects that are observed with typical neuroleptic drug treatment.

Animals↗
PubMed1994

Distinct sites of dopaminergic and glutamatergic regulation of haloperidol-induced catalepsy within the rat caudate-putamen.

Previous studies have indicated that corticostriatal glutamatergic pathways are implicated in the regulation of neuroleptic catalepsy. To obtain a better understanding of the way in which dopamine (DA) and glutamate interact within the caudate-putamen (CP) in the development of catalepsy, we investigated the regional distribution within the rat CP of the cataleptogenic effect of haloperidol and its antagonism by D(-)-2-amino-5-phosphonopentanoic acid (D(-)AP5), a selective antagonist of the N-methyl-D-aspartate (NMDA) glutamate receptor subtype. Bilateral injections of haloperidol (3 micrograms/side) into the rostral ventromedial (VM) CP induced potent catalepsy with a short latency after the injection. In contrast, only a weak cataleptic response, of slower onset, was observed after haloperidol injections into the rostral ventrolateral (VL), rostral dorsomedial (DM), or rostral dorsolateral (DL) CP, or into the nucleus accumbens. D(-)AP5 (5 micrograms/side) injected bilaterally into the dorsorostral CP (DM and DL) strongly inhibited the catalepsy induced by systemic haloperidol (1 mg/kg, i.p.), and this effect lasted longer when the drug was injected into the DM than when it was injected into the DL. D(-)AP5 did not affect haloperidol-induced catalepsy when injected into the ventrorostral (VM and VL) or intermediate dorsal CP. D(-)AP5 injected into the DM, the region most sensitive to the anticataleptic effect of the drug, had no effect on basal levels of DA and its metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, or on the modification of these levels by haloperidol in either the DM or VM. These findings suggest that, while the catalepsy resulting from DA receptor blockade by haloperidol originates mainly from the VM, the expression of this phenomenon depends on an intact glutamatergic transmission within the dorsorostral CP. In the development of neuroleptic catalepsy, the mesencephalostriatal DAergic and corticostriatal glutamatergic pathways seem to be functionally linked through an indirect, rather than a direct, interaction.

2-Amino-5-phosphonovalerate↗
PubMed1993

Dopamine D1 receptor stimulation but not dopamine D2 receptor stimulation attenuates haloperidol-induced behavioral supersensitivity and receptor up-regulation.

The effect of selective dopamine D1 and D2 receptor agonists on chronic haloperidol-treated rats was studied. Haloperidol treatment produced a 77% increase in apomorphine-induced sterotypy. The administration of the selective dopamine D1 receptor agonist SKF38393 alone or in combination with the selective dopamine D2 receptor agonist quinpirole attenuated the effect of haloperidol. Treatment with quinpirole alone did not have a significant effect on the response to haloperidol. Haloperidol did not modify the number of dopamine D1 receptors but increased that of dopamine D2 receptors. SKF38393 reversed the effect of haloperidol on dopamine D2 receptor binding. Co-administration of SKF38393 and quinpirole did not modify the increase in the number of dopamine D2 receptors induced by chronic treatment haloperidol. The results confirm a dissociation between behavioral supersensitivity and dopamine receptor up-regulation, suggesting that other mechanisms may be involved in the expression of behavioral supersensitivity.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1986

The effect of thioridazine on haloperidol induced behavioral hypersensitivity.

Behavioral Hypersensitivity (BH) to dopamine agonists occurs following chronic treatment with most neuroleptics including haloperidol. In the present study we observed that the concurrent administration of thioridazine and haloperidol prevented the development of BH. In contrast, another neuroleptic, fluphenazine, coadministered with haloperidol, potentiated the degree of BH relative to animals treated with haloperidol only. In rats already made hypersensitive by chronic treatment with haloperidol, a 4 week subsequent treatment with normal saline, thioridazine alone of thioridazine in combination with haloperidol, produced normal behavioral responsiveness. These results suggest that thioridazine prevents the development of BH and can reverse the expression of haloperidol-induced BH.

Animals↗
PubMed1991

Rebound cue state following a single dose of haloperidol.

It has been reported that chronic administration of haloperidol produces an amphetamine-like rebound cue state. The experiments reported here were designed to assess whether a similar rebound phenomenon would result from a single dose of haloperidol. Rats were trained to discriminate .5 mg/kg amphetamine from distilled water. Five groups were formed to allow testing of haloperidol's effect at 12, 18, 24, 30, and 36 hr postinjection. Each animal was given 0, .5, 1.0, and 1.5 mg/kg haloperidol at its appropriate injection time in a counterbalanced fashion with one week between each test. A shift in the dose-response function of amphetamine that occurred during these weeks, however, precluded appropriate analysis of haloperidol's effects. Given this result, a second experiment was conducted using a between-subjects design. Half of the animals were injected with 1 mg/kg haloperidol 23 hr prior to testing, whereas the others were injected with distilled water. When tested, the haloperidol group responded 33% of the time on the amphetamine-correct lever, whereas the control group responded at 20%. The observation of posthaloperidol rebound in the between-subjects study and the failure to find significant temporal patterns of rebound phenomena using a within-subjects design have both theoretical and methodological importance.

Amphetamine↗
PubMed1988

Behavioural and biochemical effects of haloperidol during the oestrous cycle of the rat.

The effects of two doses (1 and 2 mg/kg, i.p.) of haloperidol (HAL) on catalepsy, on concentrations of DA and DOPAC in frontal cortex, nucleus accumbens and striatum and on serum levels of oestradiol were investigated in intact female rats during the 4-day oestrous cycle. Catalepsy induced by haloperidol did not vary much during phases of the cycle. The turnover of DA in the cortex induced by haloperidol was significantly greater on proestrus and smaller on oestrus. The effect of haloperidol on the turnover of DA in the nucleus accumbens and in striatum was marginally affected by the oestrous cycle being greatest on oestrus. The levels of serum oestradiol were higher on proestrus and lower on oestrus. No significant differences were detected between diestrus and metestrus. After haloperidol there was a dramatic increase in serum oestradiol on oestrus, a slight increase on metestrus and diestrus and a decrease on proestrus. However, serum levels of oestradiol were not significantly different between phases of the cycle in rats treated with haloperidol. The results indicate that the oestrous cycle has a detectable influence on DAergic mechanisms in the frontal cortex and possibly in the tuberoinfudibular system, brought about by treatment with haloperidol.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1991

The enhancement of the hypomotility induced by small doses of haloperidol in the phase of dopaminergic supersensitivity in mice.

Dopaminergic supersensitivity in mice was induced by pretreatment with a single injection of haloperidol (4.8 mg/kg). After the pretreatment, further treatment with haloperidol (0.6 or 0.01 mg/kg) was made at varying intervals, and catalepsy, locomotor activity and homovanillic acid (HVA) were measured. The intensity of the supersensitivity was evaluated by enhanced apomorphine (1 mg/kg)-induced climbing behavior. Supersensitivity was displayed on the 2nd and the 4th day. The cataleptogenic effect of haloperidol (0.6 mg/kg) was significantly weakened on the 1st, 2nd and 4th days. The motor inhibitory effect of haloperidol (0.01 mg/kg) increased on the 1st, 2nd and 4th days. Homovanillic acid was measured in the striatum and the prefrontal cortex on the 2nd day. Haloperidol (0.6 mg/kg) increased the concentrations of HVA in both regions of the brain. The increase in the concentrations of HVA in the striatum was blunted after the pretreatment, but such tolerance did not develop in the prefrontal cortex. Haloperidol (0.01 mg/kg) did not influence the concentration of HVA in both regions. These results suggest that the behavioral effect of a small dose of haloperidol may be enhanced, rather than reduced, in the phase of supersensitivity.

Animals↗
PubMed1995

Induction of c-fos, jun B and egr-1 expression by haloperidol in PC12 cells: involvement of calcium.

Acute injection of haloperidol, a dopamine D2 receptor antagonist, is known to increase immediate early gene expression of the fos and jun families in rodent striatal neurons. A set of gene induction, including c-fos, jun B and TIS8/egr-1, was found when haloperidol was added to PC12 cells in culture. Electrophoretic mobility-shift assays show that haloperidol-evoked gene induction was accompanied by a transient and dose-dependent increase in AP1 and EGR-1 binding activities in these cells. Gene expression is tentatively explained by the rapid and transient increase in cytosolic free Ca2+ concentration observed upon haloperidol addition. The cytosolic calcium rise and AP1 binding activation elicited by haloperidol were dependent on extracellular Ca2+, suggesting that haloperidol exerted its effects by promoting Ca2+ entry into PC12 cells. The haloperidol-induced increase in AP1 binding activity and intracellular Ca2+ was not reproduced by two other dopamine D2 receptor antagonists, sulpiride and (+)-butaclamol.

Animals↗