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.

SourceResearch connectionFrom yearThrough year

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

At least 397 records · Page 22Linked to original sources

PubMed1987

Facilitation of the expression but not the acquisition of latent inhibition by haloperidol in rats.

In the latent inhibition (LI) paradigm, nonreinforced preexposure to a stimulus retards subsequent conditioning to that stimulus. The administration of haloperidol in both the preexposure and the conditioning stages was found to enhance LI in the conditioned emotional response (CER) procedure (Weiner and Feldon, 1986). The present experiments investigated the effects of 0.1 mg/kg haloperidol administration on LI in a two-way avoidance procedure, consisting of two stages: preexposure, in which the to-be-conditioned stimulus, tone, was repeatedly presented without reinforcement; and conditioning, in which the animals acquired a two-way avoidance response with the tone serving as the warning signal. Experiments 1 and 2 tested whether the administration of haloperidol confirmed to the preexposure stage, where learning to ignore the nonreinforced stimulus takes place, would suffice to enhance the LI effect. In Experiment 1, preexposure and conditioning were conducted 24 hr apart. LI was obtained in both the placebo and haloperidol conditions, but the effect was not more pronounced under the drug. In addition, haloperidol-treated animals exhibited impaired avoidance performance. In Experiment 2, preexposure and conditioning were given 72 hr apart. With this interval, haloperidol did not affect avoidance performance. However, also under these conditions, the magnitude of the LI effect was not larger in the haloperidol-treated groups, indicating that the administration of the drug in the preexposure stage alone did not suffice to enhance LI.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Repeated testing of rats markedly enhances the duration of effects induced by haloperidol on treadmill locomotion, catalepsy, and a conditioned avoidance response.

In the present experiments we have investigated the duration of haloperidol-induced effects in rats tested repeatedly, and in rats tested on a single occasion after drug administration. The behavioral test situations used include treadmill locomotion (speed 4 m/min), inclined grid catalepsy, two-way conditioned avoidance behavior and open field spontaneous locomotor activity. It was found that the duration of haloperidol-induced effects on treadmill locomotion, spontaneous locomotor activity, catalepsy and a conditioned avoidance response (doses: 0.32, 0.32, 1.25 and 0.2 mg/kg IP, respectively) was about 2 hr or less in animals observed once only ("independent procedure"). With the possible exception for locomotor activity, the duration of haloperidol-induced effects was considerably prolonged, up to 8 hr depending on the test situation, in animals observed repeatedly after the administration of haloperidol in the same doses ("dependent procedure"). The enhanced duration by the dependent procedure is probably not caused by handling stress since the enhanced duration of haloperidol-induced effects in some of the behavioral tests were only noted in animals tested repeatedly in one particular test, and not in animals given the repeated pretests in another situation. Furthermore, it was not possible to relate the enhanced duration of haloperidol-induced effects by repeated testing to changes in striatal DA metabolism as evaluated by measurements of DOPAC, HVA and DA. It was found that the treadmill test 2-4 hr after haloperidol (0.12-0.32 mg/kg IP), at certain doses and time intervals produced an increase in DA turnover [(DOPAC + HVA)/DA], but this increase was the same in both procedures (dependent and independent).(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗

PubMed1990

Similar behavioral and biochemical effects of long-term haloperidol and caerulein treatment in albino mice.

Behavioral and biochemical experiments on male albino mice have revealed similar effects after the cessation of repeated (15 days) haloperidol (0.5 mg/kg daily IP) and caerulein (0.1 mg/kg daily SC) treatment. Tolerance developed to the action of muscimol (a GABA-A agonist, 1 mg/kg IP), caerulein (a CCK-8 agonist, 15 micrograms/kg SC) and flumazenil (a benzodiazepine antagonist, 10 mg/kg IP). Muscimol and caerulein were not able to suppress the motor activity of mice after 15 days treatment with haloperidol and caerulein. Flumazenil, which increased motor activity in saline-treated animals, also failed to affect activity after extended haloperidol or caerulein treatment. In contrast, the motor excitation induced by amphetamine (an indirect dopamine agonist, 3 mg/kg IP) was increased after haloperidol or caerulein administration. In radioligand binding studies the density of dopamine-2-receptors in striatum, opioid receptors in mesolimbic structures, and benzodiazepine and GABA-A receptors in brainstem was significantly elevated after long-term haloperidol or caerulein treatment. Simultaneously, the number of CCK-8, benzodiazepine and GABA-A receptors in cerebral cortex was decreased. It is probable that CCK-8-ergic mechanisms are involved closely in the action of repeated haloperidol treatment. CCK-8 seems to modulate the action of haloperidol through altering the sensitivity of dopamine, opioid, GABA-A and benzodiazepine receptors.

Amphetamine↗

PubMed1992

Bilateral neurochemical changes induced by unilateral cerebral haloperidol administration: evidence for cerebral asymmetry in the rat.

Bilateral alterations in dopamine metabolism were determined in the striatum, olfactory tubercle, and frontal cortex of rats pretested for circling behavior. Dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), norepinephrine, and 5-hydroxyindole-3-acetic acid (5-HIAA) were measured by high-performance liquid chromatography 15 min after right or left intracarotid infusion of haloperidol. Concentrations of DOPAC and HVA were significantly increased in the striatum and frontal cortex ipsilateral to the side of haloperidol infusion, regardless of whether it was right or left. In contrast, the concentrations of these metabolites were unchanged in the olfactory tubercle after a right side infusion, but bilateral increases were evident after a left side infusion. Higher levels of DOPAC and HVA were also apparent in the left striatum and olfactory tubercle after intravenous jugular administration of haloperidol. Dopamine levels were significantly lower in the left striatum and right olfactory tubercle after intravenous haloperidol infusions. 5-HIAA concentrations were higher in the left olfactory tubercle following left side infusions of haloperidol. These data indicate that unilateral cerebral administration of haloperidol induces asymmetric and side-dependent alterations in dopamine and serotonin metabolites. These differences appear to be due to intrinsic variations in the sensitivity to haloperidol, but are not associated with the direction of circling behavior.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1990

Simple disturbance of the dam in the neonatal period can alter haloperidol-induced catalepsy in the adult offspring.

Three experiments were performed to determine whether apparently minimal disturbances of dams and litters would influence haloperidol-induced akinesia. In Experiment I, Long-Evans hooded rats (a) were left unmanipulated, (b) received nestcage relocation and observation, (c) received nestcage relocation/observation and maternal separation, or (d) received nestcage relocation/observation and pup handling. The male adult offspring received open-field testing and later received forepaw-on-dowel catalepsy testing following saline, morphine (20 mg/kg), or haloperidol (2 mg/kg). In Experiment II, hooded rats received (a) no manipulation, (b) nestcage relocation, (c) maternal separation, or (d) pup handling. At weaning, dams were tested in the open-field. Activity wheel locomotion of the offspring was assessed following saline or haloperidol for 3 days/week for 3 weeks; then, 5 and 7 days later, rats received haloperidol (0.5 mg/kg) and catalepsy testing. In both experiments, manipulations involving the dam reduced the offsprings' haloperidol-induced catalepsy, but, in Experiment II, a history of haloperidol administration distinguished between the effects of nestcage relocation and maternal separation. In Experiment III, Swiss albino mice received (a) no treatment, (b) nestcage relocation and maternal separation, (c) relocation/separation and mild cold stress of pups, (d) relocation/separation and pup handling, or (e) relocation/separation and severe cold stress of pups. Adult male mice received saline or haloperidol (2.5 mg/kg) and inclined grid catalepsy testing. Mice receiving relocation/separation and mice receiving relocation/separation and severe cold stress showed enhanced catalepsy versus control mice. Thus, it was concluded that seemingly innocuous events in infancy can influence the intensity of extrapyramidal side effects of neuroleptics in adulthood.

Animals↗

PubMed1993

Anti-idiotypes against an anti-haloperidol antibody bind to sigma receptors.

Anti-idiotypic monoclonal antibodies that interact with the binding site of sigma receptors were generated. First, BALB/c mice were immunized with a haloperidol-bovine serum albumin conjugate, and monoclonal anti-haloperidol antibodies that recognize the piperidinyl moiety of haloperidol molecule were obtained. Second, for generation of anti-idiotypic antibodies, BALB/c mice were immunized with the anti-haloperidol monoclonal antibodies coupled to keyhole limpet hemocyanin. Anti-idiotypic antisera and three hybridomas secreting anti-idiotypic monoclonal antibodies were obtained. All of them were shown to inhibit [3H]haloperidol binding to the anti-haloperidol antibodies. The anti-idiotypes were potent in displacing the binding of [3H]haloperidol to rat brain sigma receptors. Furthermore, they significantly immunoprecipitated the sigma receptors from a detergent-solubilized preparation. These findings demonstrate the generation of anti-idiotypic monoclonal antibodies specifically interacting with membrane-bound and solubilized sigma receptors.

Animals↗

PubMed1989

Determination of plasma haloperidol concentrations by radioreceptor assay in schizophrenia: clinical utility.

1. Haloperidol concentrations were determined by radioreceptor assay (RRA) and prolactin concentrations were measured in 20 patients diagnosed as schizophrenia (DSM-III). 2. The patients were treated with a fixed dose of haloperidol for 21 days. 3. Our results suggest the existence of a curvilinear relationship, in the form of an inverted U, between stable haloperidol levels and clinical improvement assessed by total BPRS score. 4. We also found a curvilinear relationship between the improvement observed in positive symptoms and state steady levels. 5. No relationship was seen between improvement in negative symptoms and state steady levels. 6. An interval of optimal haloperidol concentration was found: 8.1 ng/ml to 19.6 ng/ml. 7. No relation was found between the dose of haloperidol administered and plasmatic concentration, nor between haloperidol and prolactin levels. 8. Our findings suggest that haloperidol concentrations determined by RRA have clinical utility as predictors of response in schizophrenia.

Adolescent↗

PubMed1992

Haloperidol differentiates smooth muscle contractions induced by release of intracellularly stored Ca and by influx of extracellular Ca.

1. The effects of haloperidol on smooth muscle contraction induced by carbachol, histamine, high K or caffeine in the presence or absence of extracellular Ca were investigated. 2. In the presence of extracellular Ca, the maximal contraction induced by carbachol was reduced by haloperidol, while that by histamine or high K was much less affected. 3. In Ca-free solution, contraction induced by histamine was extremely reduced by haloperidol, while that by carbachol was not affected. 4. These results suggest that haloperidol selectively inhibited signal transduction processes from activation of muscarinic acetylcholine receptors to influx of extracellular Ca and from activation of histamine H1-receptors to release of intracellularly stored Ca. 5. Caffeine-induced contraction in Ca-free solution was markedly potentiated by haloperidol, although haloperidol did not elicit contraction in Ca-free solution by itself. 6. These results suggest that haloperidol increased the sensitivity of Ca-induced Ca release channels to caffeine.

Animals↗

PubMed1992

Neuroleptics increase c-fos expression in the forebrain: contrasting effects of haloperidol and clozapine.

The mechanisms by which the atypical neuroleptic clozapine produces its therapeutic effects in the treatment of schizophrenia without causing the extrapyramidal side effects that are characteristic of most antipsychotic drugs remain unclear. Recently, a single injection of the typical antipsychotic haloperidol has been shown to increase c-fos expression in the striatum [Dragunow et al. (1990) Neuroscience 37, 287-294]. C-fos is a proto-oncogene that encodes a 55,000 mol. wt phosphoprotein, Fos, which is thought to assist in the regulation of "target genes" containing an AP-1 binding site. Because a wide variety of physiological and pharmacological stimuli increase c-fos expression, it has been proposed that Fos immunohistochemistry might be useful in mapping functional pathways in the central nervous system. The present experiments examined some potential neuroanatomical differences in the actions of clozapine and haloperidol by comparing their effects on c-fos expression in the medial prefrontal cortex, nucleus accumbens, striatum and lateral septum. The effects of the selective dopamine receptor antagonists SCH 23390 (D1) and raclopride (D2) were also examined. Haloperidol (0.5, 1 mg/kg) and raclopride (1, 2 mg/kg) produced large increases in the number of Fos-containing neurons in the striatum and nucleus accumbens. SCH 23390 (0.5, 1 mg/kg) reduced the number of Fos-positive neurons in the nucleus accumbens and striatum, and had no effect in the other regions. Neither haloperidol nor raclopride increased the number of Fos-positive neurons in the medial prefrontal cortex. Haloperidol, but not raclopride, produced a modest increase in c-fos expression in the lateral septal nucleus. Clozapine (10, 20 mg/kg) was without effect in the striatum; however, it significantly increased the number of Fos-positive neurons in the nucleus accumbens, medial prefrontal cortex and lateral septal nucleus. Destruction of mesotelencephalic dopaminergic neurons with 6-hydroxydopamine abolished the increase in Fos expression in the nucleus accumbens and striatum produced by haloperidol and raclopride, and also blocked the clozapine-induced increase in the nucleus accumbens. However, the inductive effects of clozapine and haloperidol on c-fos expression in the lateral septal nucleus and of clozapine in the medial prefrontal cortex were not affected by the 6-hydroxydopamine lesions. These results suggest that clozapine's unique therapeutic profile may be related to its failure to induce Fos in the striatum as well as its idiosyncratic actions in the lateral septum and medial prefrontal cortex. The effects of clozapine in these latter regions do not appear to be mediated by dopaminergic mechanisms.

Animals↗

PubMed1987

Genotypic influences on pituitary responsiveness to haloperidol in mice.

Previous studies from this laboratory demonstrated that CBA/J mice have impaired striatal dopaminergic supersensitivity in response to subchronic haloperidol administration. Others have speculated that the peripheral hyperprolactinemia produced by haloperidol is necessary for the striatal dopamine receptor supersensitization produced by dopamine antagonists. In the present experiments, we tested the hypothesis that the impaired supersensitization response to haloperidol in CBA/J mice was secondary to an impaired hyperprolactinemic response by comparing the CBA/J mice with other mice that show normal supersensitization responses: the BALB/cJ and C57BL/6J strains. Acute haloperidol treatments increased serum prolactin levels 60 min later in all three strains, with the greatest response in CBA/J mice. After longer haloperidol treatment (2 or 21 days), serum prolactin remained elevated in CBA/J and, to a lesser extent, in C57BL/6J mice; levels remained low throughout treatment in BALB/cJ mice. Although, the basal density of pituitary dopamine receptors [( 3H]spiperone or D-2 binding sites) was greater in CBA/J than BALB/cJ mice, only BALB/cJ mice showed increased pituitary D-2 binding sites following chronic haloperidol administration. Taken together with previous studies of dopamine and noradrenaline receptors in these mouse strains, we conclude that CBA/J mice have a generalized impairment in their supersensitization responses to pharmacologic blockade of receptors. These data do not support the involvement of prolactin in haloperidol-induced dopamine receptor up-regulation.

Animals↗

PubMed1989

Haloperidol given chronically decreases basal dopamine in the prefrontal cortex more than the striatum or nucleus accumbens as simultaneously measured by microdialysis.

Simultaneous microdialysis was performed in the prefrontal cortex, striatum, and the caudal region of the nucleus accumbens using implanted guide shafts with removable microdialysis probes. Extracellular dopamine (DA), dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) were measured in response to acute and chronic haloperidol, an antipsychotic drug. Six rats received haloperidol (0.5 mg/kg, IP) while changes in DA and its metabolites were monitored for six hours. Then the microdialysis probes were removed and daily injections of haloperidol were given for 28 more days. Next the probes were reinserted, and a final haloperidol challenge was given. A control group of six rats was treated the same way but with saline. The first injection of haloperidol increased extracellular DA, DOPAC and HVA proving increased turnover in all three regions. A month later, after chronic treatment, basal DA and its metabolites decreased in just the cortex. DOPAC and HVA also decreased in the cortex and striatum, suggesting a decrease in turnover at these two sites. None of these changes occurred in the accumbens. The last haloperidol challenge after chronic treatment no longer increased extracellular DA in any of the three sites, but increased production of metabolites was still detectable. This suggests a lack of DA responsiveness in all three sites. In summary, chronic haloperidol affected each of the regions differently; DA metabolites decreased in the STR and PFC; basal DA decreased in the PFC.

Animals↗

PubMed1993

Haloperidol affects stimulus-dependent strategies and not reward-dependent strategies.

In order to investigate effects of haloperidol on response strategies, rats were confronted with an unsolvable discrimination problem after being injected with haloperidol (0.1 mg/kg, IP) or its solvent. The results showed that haloperidol-treated rats displayed systematic behaviour to a lesser degree than the control rats. Haloperidol did not affect reward-dependent response strategies. However, haloperidol did affect stimulus-dependent response strategies. Haloperidol-treated rats showed more response strategies based on visual or auditory cues, and less spatial response strategies than control rats. It is concluded that this differential effect of haloperidol is the consequence of the different nature of the stimuli (discretely present visual and auditory stimuli versus constantly present spatial stimuli).

Acoustic Stimulation↗

PubMed1994

Dopamine increase in the prefrontal cortex correlates with reversal of haloperidol-induced catalepsy in rats.

The mechanism by which forced swimming reverses, haloperidol-induced catalepsy was examined by measuring dopamine (DA) turnover in the nucleus accumbens-ventromedial caudate (NAC-C) and the prefrontal cortex (PFC) in rats. DA and its metabolites 3,4-dihydroxiphenylacetic acid (DOPAC) and homovanillic acid (HVA) were assessed by microdialysis and high pressure liquid chromatography with electrochemical detection (HPLC-ED) after systemic administration of a cataleptic dose of haloperidol (5 mg/kg) or saline. Haloperidol-induced catalepsy was temporarily suppressed by forced swimming. Haloperidol-treated rats showed an increase of DA, DOPAC, and HVA overflow in the PFC and the NAC-C. This increase was greater in the PFC of rats that were forced to swim. Rats that were not treated with haloperidol but were forced to swim (control group) showed an increase of DA, DOPAC, and HVA in the PFC but not in the NAC-C. Zero micrograms, 5 micrograms, 10 micrograms, and 20 micrograms of DA was bilaterally injected in the PFC of cataleptic rats to evaluate the hypothesis that DA in the PFC reverses catalepsy. Haloperidol-induced catalepsy was diminished by bilateral microinjections of 10 micrograms and 20 micrograms but not by 5 micrograms of DA in the PFC. The higher the dose of DA, the longer the decrease of catalepsy. These results suggest that an increase of DA turnover in the PFC might mediate temporal suppression of haloperidol-induced catalepsy. The mechanism by which the mesocortical DA system reduces catalepsy is discussed.

3,4-Dihydroxyphenylacetic Acid↗

PubMed2005

Haloperidol can increase responding to both discrete and contextual cues in trace conditioned rats.

Haloperidol has been shown to enhance attentional selectivity in conditioning procedures. For example, in latent inhibition (LI) it improves animals' ability to treat as irrelevant, stimuli that have previously been presented without consequence. The present study tested whether this finding would generalize to other procedures that present animals with weak predictors. We therefore used a trace conditioning procedure to present rats with a conditioned stimulus (CS) weakened through temporal discontiguity (rather than preexposure in LI) and a flashing light background provided an alternative experimental stimulus. In Experiment 1, a noise CS was paired contiguously (at '0 s') with food or at a 10 s trace interval. In Experiment 2, the trace interval was lengthened to 20 s. In both experiments, haloperidol treatment generally reduced responding in 0 s contiguous groups. By contrast, 0.03 mg/kg haloperidol enhanced conditioning, selectively, to the weakly predictive trace CS, though it was without effect on responding within the trace interval. In addition, again at 0.03 mg/kg, haloperidol significantly increased excitatory conditioning to contextual stimuli in trace groups relative to contiguous groups. At the shorter (10 s) Experiment 1 trace, this result was shown in the extinction test of conditioning to the background stimulus. At the longer (20 s) Experiment 2 trace, this result was shown in the acquisition of responding to the box context in the inter-trial-interval. The demonstration that low dose haloperidol can increase conditioning is novel. This increase was seen selectively with stimuli (both trace-conditioned and contextual) that should have been treated as weak predictors so these results are contrary to what was expected on the basis of haloperidol effects on stimuli weakened through pre-exposure. The possibility that increased contextual conditioning could be relevant to the interpretation of haloperidol-induced enhancement of LI is discounted. However, it is suggested that this result could nonetheless reflect cognitive enhancement.

Acoustic Stimulation↗

PubMed2005

Acute and continuation risperidone monotherapy in bipolar mania: a 3-week placebo-controlled trial followed by a 9-week double-blind trial of risperidone and haloperidol.

In a randomized, double-blind trial, patients with acute bipolar mania received 1-6 mg/day of risperidone, 2-12 mg/day of haloperidol, or placebo for 3 weeks, followed by double-blind risperidone or haloperidol for 9 weeks. Of 438 patients, 154 were randomized to risperidone, 144 to haloperidol, and 140 to placebo. The mean+/-S.D. modal doses were 4.2+/-1.7 mg/day of risperidone and 8.0+/-3.6 mg/day of haloperidol during the initial 3-week phase and 4.1+/-1.8 and 7.4+/-3.7 mg/day during the 12-week period. At week 3, mean Young Mania Rating Scale (YMRS) score reductions from baseline were significantly greater in patients receiving risperidone than placebo (p<0.001). Differences between risperidone and haloperidol on this efficacy measure were not significant. Further reductions in YMRS scores were seen in patients receiving risperidone or haloperidol during the subsequent 9 weeks. No unexpected adverse events were reported. Extrapyramidal disorder and hyperkinesias, the most commonly reported adverse events with antipsychotic use, occurred less frequently with risperidone than haloperidol. We conclude that risperidone monotherapy was an effective and well-tolerated treatment for bipolar mania and that efficacy was maintained over the long term.

Adolescent↗

PubMed2006

Haloperidol and atypical antipsychotics share a same action of decreasing P75(NTR) mRNA levels in PC12 cells.

P75(NTR) is a common neurotrophin receptor which binds all neurotrophins with similar affinities and has been shown to be capable of mediating programmed cell death. In this study, we investigated effects of the antipsychotic drugs (APDs) haloperidol, clozapine, quetiapine, and risperidone on p75(NTR) mRNA levels in PC12 cells. Haloperidol is a prototype of typical APDs, and the other three drugs are atypical APDs, which are effective in reducing negative symptoms and cognitive deficits of schizophrenia, cause less side effects, and are more tolerable compared to haloperidol. PC12 cells were cultured with various concentrations of haloperidol, clozapine, quetiapine, or risperidone, in their media. After culture for 48h, the cell viabilities and p75(NTR) mRNA levels were measured. It was shown that both haloperidol and the atypical APDs used in this study deceased p75(NTR) mRNA levels in PC12 cells in a dose dependent manner, while not affecting cell viabilities. In further experiments, doses that produced significant/greatest effects were chosen and provided in the culture media for various periods. Decreases in p75(NTR) mRNA levels were observed in cultures treated for 12h with quetiapine, 24h with clozapine or risperidone, or for 48h with haloperidol. These results suggest that both haloperidol and atypical APDs have the same action of decreasing p75(NTR) mRNA levels in PC12 cells. Although the underlying molecular mechanism of this action remains to be elucidated, this finding is particularly relevant given the neurodevelopmental deficits associated with schizophrenia and important roles of p75(NTR) in mediating cell death.

Animals↗

PubMed2006

Chronic high-dose haloperidol has qualitatively similar effects to risperidone and clozapine on immediate-early gene and tyrosine hydroxylase expression in the rat locus coeruleus but not medial prefrontal cortex.

Acute administration of clozapine has been reported to activate the locus coeruleus (LC) and beta-adrenoceptor-dependent Fos immunoreactivity in the medial prefrontal cortex (mPFC) in rodents. Haloperidol is reported to exhibit a similar acute effect on LC firing and beta-adrenoceptor dependent Fos immunoreactivity in the mPFC but only at high doses. We compared the effects of chronic 4-week treatment with risperidone (1mg/kg/day s.c.), clozapine (10mg/kg/day s.c.) or a high dose of haloperidol (4mg/kg/day s.c.) on immediate-early gene protein (c-Fos, Egr-1 and Egr-2) and tyrosine hydroxylase (TH) expression. In the mPFC, haloperidol decreased, whereas clozapine increased, c-Fos immunoreactivity. Only haloperidol increased Egr-1 immunoreactivity. There was no significant effect on Egr-2 immunoreactivity. In the LC, both Egr-1 and Egr-2 expression was down regulated by all three antipsychotics. Clozapine and risperidone increased TH immunoreactivity in both mPFC and LC. Haloperidol caused a smaller increase in TH expression in the LC, but did not alter expression in the mPFC. In conclusion, despite qualitatively similar effects in the LC, chronic treatment with haloperidol had different effects to clozapine and risperidone in the mPFC. This may relate to the reported advantage of clozapine and risperidone over haloperidol against prefrontal cortical-dependent cognitive and negative symptoms.

Animals↗

PubMed2005

Effects of donepezil, nicotine and haloperidol on the central serotonergic system in mice: implications for Tourette's syndrome.

We have previously reported that acute and chronic donepezil and nicotine administration significantly attenuate DOI-induced head twitch response (HTR) in mice. This behavior, primarily mediated by stimulation of 5-HT2A receptors, has been proposed to model tic symptoms seen in Tourette's syndrome (TS). Haloperidol, a drug widely used to treat symptoms of TS, has also been reported to reduce DOI-induced head shakes in rodents when administered acutely. These findings suggest an inhibitory interaction of these drugs with 5-HT2A receptors. To test this hypothesis, we evaluated the effects of chronic donepezil, nicotine and haloperidol on expression levels of 5-HT2A mRNA and 5-HT2A receptor density in select brain regions. Initially, we established a dose-response relationship for the acute and chronic haloperidol and DOI-induced HTR. Male ICR mice were treated twice daily with donepezil (0.1 mg/kg), nicotine (0.5 mg/kg), and once daily with haloperidol (0.4 mg/kg) for 14 days and were sacrificed 16-18 h after the last injection. These drug regimens were chosen because of their significant effects on DOI-induced HTR. Donepezil significantly increased 5-HT2A mRNA level, but not the receptor density in the striatum. In the midbrain, donepezil significantly decreased the receptor density without affecting the 5-HT2A mRNA level. In the frontal cortex, only haloperidol significantly reduced the 5-HT2A receptor density. The cortex was the only area where donepezil, nicotine and haloperidol significantly reduced the 5-HT2A receptor density. The results suggest that the anti-tic properties of donepezil, nicotine and haloperidol in this paradigm might be due to antagonism of cortical 5-HT2A receptors. Thus, further investigation of involvement of cortical 5-HT2A receptors in TS as well as evaluation of selective 5-HT2A receptor antagonists in this disorder is warranted.

Amphetamines↗