Chronic treatment with chlorpromazine, thioridazine or haloperidol increases striatal enkephalins and their release from rat brain

Herman, Zbigniew S.; Huzarska, M; Kmieciak-Kołada, K; Kowalski, Jan

doi:10.1007/bf02244563

Cited by 17 publications

(8 citation statements)

References 47 publications

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“…These results are consistent with findings from many other groups who have demonstrated that typical-but not atypical-antipsychotics increase enkephalin content and mRNA levels in the caudate-putamen (Herman et al 1991;Angulo 1992; Tissue levels (fmol/per mg wet weight) were determined 24 hours after the drug or vehicle application. In the prefrontal cortex, absolute values were for enkephalin (7 Ϯ 1), for secretoneurin (32 Ϯ 4.5), and for PE-11 (42 Ϯ 3.8).…”

Section: Neurochemical Measuressupporting

confidence: 91%

Further Evidence that Behavioral Tests and Neuropeptide mRNA and Tissue Level Alterations Can Differentiate between Typical and Atypical Antipsychotic Drugs

Bauer

Mayr

Lederer

et al. 2000

Neuropsychopharmacology

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This study was designed to compare some behavioral and biochemical effects of chronic treatment with a range of antipsychotic drugs. Gene expression of enkephalinAntipsychotic drugs are sometimes referred to as "atypical" if they demonstrate the ability to produce an antipsychotic action in most patients but with significantly less extrapyramidal side effects than classical (typical) antipsychotics (Fleischhacker and Hummer 1997). Lately, this distinction between "typical" and "atypical" antipsychotics has become the focus for much research aimed at establishing the pharmacological characteristics that serve to distinguish atypical antipsychotic drugs from the typical ones (Arnt and Skarsfeldt 1998). For example, in animals, acute and chronic treatment with these compounds causes distinct behavioral changes and alterations in the expression of different genes.Alterations in the biosynthesis of synaptic proteins and their mRNAs can be used to investigate changes in neuronal activity following different neuronal stimuli (MacArthur and Eiden 1996). Haloperidol increases tissue levels of enkephalin and the expression of mRNA (Normand et al. 1987;Romano et al. 1987) in medium spiny striatal neurons which are associated with the dopamine 2 receptor (Le Moine et al. 1991) whereas clozapine, the prototypical "atypical" antipsychotic, does not induce catalepsy and does not lead to an increased enkephalin gene expression in the striatum (Mercugliano and Chesselet 1992). Consequently, antipsychotics which do not induce catalepsy appear unlikely to increase enkephalin biosynthesis (Augood et al. 1993;Mijnster et al. 1998). Therefore, both behavioral changes and a distinct pattern of gene expression may be used to predict an atypical profile for an antipsychotic compound.The prefrontal cortex is an important brain area in schizophrenia research (Knable and Weinberger 1997;O'Donnell and Grace 1998). In animals, antipsychotic treatment causes an induction of immediate early genes in various brain areas including the prefrontal cortex. In this region, acute application of haloperidol or clozapine induces a differential expression of immediate early genes (Nguyen et al. 1992;Robertson and Fibiger 1992;Deutch and Duman 1996). Therefore, a different mechanism of action was postulated for haloperidol or clozapine treatment. However, most of these experiments investigated the induction of early genes after acute treatment.Chromogranin A, chromogranin B, and secretogranin II belong to the chromogranin family which are large protein molecules found in large dense core vesicles. They are endoproteolytically processed to smaller peptides, and are released after neuronal stimulation (Huttner et al. 1991). The distribution of chromogranin B (Mahata et al. 1991;Kroesen et al. 1996), secretogranin II mRNA, and their immunoreactivity (Marksteiner et al. 1993a) have been studied in rat brains. The biosynthesis of chromogranins is regulated by different stimuli (Shen and Gundlach 1996). For example, ten days of treatment with clozapine or hal...

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Section: Neurochemical Measuressupporting

confidence: 91%

Further Evidence that Behavioral Tests and Neuropeptide mRNA and Tissue Level Alterations Can Differentiate between Typical and Atypical Antipsychotic Drugs

Bauer

Mayr

Lederer

et al. 2000

Neuropsychopharmacology

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“…Previous studies have shown that neuroleptic treatment produces a time-dependent increase in tissue enkephalin levels (Auchus and Pickel, 1992;Chou et al, 1984;Hong et al, 1979;Mochetti et al, 1987;Sabhol et al, 1983) and enkephalin release (Llorens-Cortes et al, 1991). Striatal levels of enkephalin mRNA remain elevated for up to 3 months during chronic neuroleptic treatment (Abood et al 1990;Angulo, 1992;Angulo et al, 1986Angulo et al, ,1990Herman et al, 1991;LeMoine et al, 1990;Morris and Hunt, 1991;Petrack et al, 1990;Romano et al, 1987;Sivam et al, 1986;Tang et al, 1983). The initial elevations in mRNA, however, become less pronounced over time (Reimer et al, 1992;Vernier et al, 1988).…”

Section: D2mentioning

confidence: 98%

Alterations in mRNA levels of D2 receptors and neuropeptides in striatonigral and striatopallidal neurons of rats with neuroleptic‐induced dyskinesias

Egan

Hurd

Hyde

et al. 1994

Synapse

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Chronic neuroleptic treatment in rat produces vacuous chewing movements (VCMs), analogous to TD in humans. We hypothesized that these hyperkinetic movements were due to alterations in striatonigral and striatopallidal GABAergic spiny II neurons. Rats were treated for 36 weeks with haloperidol decanoate and withdrawn for 28 weeks. Striatonigral and striatopallidal neurons were assessed using in situ hybridization histochemistry for mRNA levels of D1 and D2 dopamine receptors, preproenkephalin (ENK), prodynorphin (DYN), protachykinin (substance P), and glutamate decarboxylase (GAD67) in the dorsolateral and ventromedial striatum as well as the nucleus accumbens. Rats that did not develop VCMs (-VCM) had increased D2 receptor and DYN mRNA, and reduced substance P mRNA in the dorsolateral striatum. Rats with persistent VCMs (+VCM) had increased D2 receptor, ENK, and DYN mRNA in both striatal regions, and increased ENK and DYN mRNA in the nucleus accumbens, compared with controls. Relative to -VCM rats, however, +VCM rats only had increased ENK mRNA in the nucleus accumbens. Considering the overall pattern of mRNA changes, the data suggest that alterations in both the D1-mediated striatonigral and the D2-mediated striatopallidal pathways play a role in the expression of the VCM syndrome. To the extent that gene expression parallels changes in neuronal activity, this implies that the VCM syndrome is associated with increased activity in both pathways.

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“…Our finding that both antipsychotic drugs affect striatal preproenkephalin-A mRNA is in line with previous studies demonstrating that haloperidol and a wide range of other antipsychotics induce increases of ppEnk-A mRNA and peptide levels of varying magnitudes (Hong et al, 1980;Tang et al, 1983;Angulo et al, 1990b;Houdi and Van Loon, 1990;Herman et al, 1991). 1 Animals received drug treatment for 14 days and were decapitated 16 h after the last treatment.…”

Section: Comparison Of the Actions Of Risperidone And Haloperidol On mentioning

confidence: 46%

Effects of risperidone and haloperidol on tachykinin and opioid precursor peptide mRNA levels in the caudate-putamen and nucleus accumbens of the rat

Mijnster

Schotte

Docter

et al. 1998

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We investigated whether the two output pathways of the striatum are differently affected by the novel atypical drug risperidone and the conventional typical antipsychotic drug haloperidol. To this end, changes in mRNA levels of preproenkephalin-A, preproenkephalin-B, and preprotachykinin were determined in the rat striatum following chronic drug treatment for 14 days, using quantitative in situ hybridization. Furthermore, we studied the contribution of the dopamine D2 and serotonin 5-HT2A antagonist components of risperidone in establishing its effects on neuropeptide mRNA levels in the striatum. The results showed that both risperidone and haloperidol had major effects on the preproenkephalin-A mRNA and thus on the indirect striatal output route, whereas they had minor effects on preproenkephalin-B and preprotachykinin mRNA, contained by the direct output route. When both drugs were administered in the same dose, preproenkephalin-A mRNA was much more elevated by haloperidol than by risperidone. However, when doses of risperidone and haloperidol were modified to attain comparable dopamine D2 receptor occupancy, the drugs had comparable effects on preproenkephalin-A mRNA levels. It was further found that 5-HT2A/C receptor blockade with ritanserin had only modest effects on preproenkephalin-B and preprotachykinin mRNA levels and did not affect preproenkephalin-A mRNA levels. We conclude that risperidone and haloperidol, administered in the same dose, differently affect the striatal output routes. Furthermore, the results suggest that the effects of risperidone on neuropeptide mRNA levels are fully accounted for by its D2 antagonism and that no indication exists for a role of 5-HT2A receptor blockade in this action.

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Chronic treatment with chlorpromazine, thioridazine or haloperidol increases striatal enkephalins and their release from rat brain

Cited by 17 publications

References 47 publications

Further Evidence that Behavioral Tests and Neuropeptide mRNA and Tissue Level Alterations Can Differentiate between Typical and Atypical Antipsychotic Drugs

Further Evidence that Behavioral Tests and Neuropeptide mRNA and Tissue Level Alterations Can Differentiate between Typical and Atypical Antipsychotic Drugs

Alterations in mRNA levels of D2 receptors and neuropeptides in striatonigral and striatopallidal neurons of rats with neuroleptic‐induced dyskinesias

Effects of risperidone and haloperidol on tachykinin and opioid precursor peptide mRNA levels in the caudate-putamen and nucleus accumbens of the rat

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