Tiagabine inhibits haloperidol-induced oral dyskinesias in rats

Gao, Xuemin; Kakigi, Tatsuya; Friedman, Mitchell; Tamminga, Carol A.

doi:10.1007/bf01283031

Cited by 18 publications

(9 citation statements)

References 15 publications

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“…Both Long-Evans animals and Wistar rats behaved differently from Sprague-Dawley rats with respect to these characteristics. After this initial descriptive experiment, we have applied this same metholodology in several subsequent experiments to test the pharmacologic characteristics of this animal paradigm (Shirakawa and Tamminga 1994;Kakigi et al 1995;Gao et al 1994;Gao and Tamminga 1996). We assume that the careful duplication of this animal preparation procedure within our laboratory will reproduce the behavioral characteristics of this paradigm.…”

Section: Methodsmentioning

confidence: 99%

Chronic Olanzapine or Sertindole Treatment Results in Reduced Oral Chewing Movements in Rats Compared to Haloperidol

Gao

Sakai

Tamminga

1998

Neuropsychopharmacology

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Chronic haloperidol treatment typically produces late-onset, purposeless oral chewing movements in laboratory rats with a prevalence of 40 to 60%. Chronic clozapine does not produce these movements. Based on the phenomenologic and pharmacologic similarities between these rat chewing movements and human tardive dyskinesia (TD), the animal movements are often used as a model of tardive dyskinesia (TD). Here we report results of the association of oral chewing movements in rats withTraditional antipsychotics, such as haloperidol or fluphenazine, induce purposeless oral chewing movements in rats when they are administered chronically (Clow et al. 1980;Ellison et al. 1987;Waddington 1990;Glenthoj and Hemmingsen 1989). These dyskinesias appear gradually, and they occur in only some of the animals. Because characteristics of these neuroleptic-induced rat movements parallel certain features (although not all) of the human neuroleptic-induced dyskinetic syndrome tardive dyskinesia (TD), they are often used in its study.General criteria for using an animal preparation as a model for a human condition have previously been proposed (McKinney and Bunney 1969) and refined (Weiss and Kilts 1995). Scientists have stressed that the most critical elements for comparison are similarities in etiology, phenomenology, biochemistry, and pharmacology between the animal and the human condition. The etiology of these rat oral dyskinesias (i.e., the chronic antipsychotic treatment) matches the etiology of TD, as do some of the demographic aspects of the rat movements, such as slow symptom onset, delayed offset, and jerky quality (Tamminga et al. 1990;Waddington 1990). Moreover, whereas traditional neuroleptics cause these purposeless movements in rats and tardive dyskinesia in humans, clozapine fails to produce dyskinesias in ei- Chronic Olanzapine or Sertindole in Rats 429 ther rats or humans (Gunne et al. 1982;Kakigi et al. 1995). The difficulty of distinguishing types of antipsychotic-induced movements in rats, along with the limited oral distribution of the movements in rats, and disagreements about the anticholinergic suppressability of the rat movements, have maintained a proper skepticism about using this preparation without reservation as an animal model of human TD. In this report, we have attempted to expand the pharmacology of these rat dyskinesias by testing whether two of the new antipsychotic drugs, olanzapine and sertindole, which have known low acute motor side effect profiles in humans, would induce purposeless oral chewing in rats.Olanzapine is a new antipsychotic drug developed by Lilly Laboratories, Inc., a thio[1,5]benzo-diazepine (Bymaster et al. 1996). It has potent antipsychotic actions in schizophrenic psychosis, comparable to traditional neuroleptics, and is active against both positive and negative symptoms (Beasley et al. 1996). One of the unusual characteristics of olanzapine is its low potency in producing Parkinsonian side effects and akathisia in humans. Olanzapine is a clozapine-like drug with respect to i...

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Section: Methodsmentioning

confidence: 99%

Chronic Olanzapine or Sertindole Treatment Results in Reduced Oral Chewing Movements in Rats Compared to Haloperidol

Gao

Sakai

Tamminga

1998

Neuropsychopharmacology

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“…Animals included in this analysis came from eight distinct studies conducted over a 7-year (19881994) year time period (Tamminga et al 1990;Gao et al 1994Gao et al , 1996Shirakawa and Tamminga 1994;Kakigi et al 1995). Each study at the time it was carried out included both a control and a haloperidol group; all utilized the same dose of haloperidol (1.5 mg / kg per day), the same dosing technique (oral, with drinking water) and the same blind behavioral assessment detailed below.…”

Section: Animalsmentioning

confidence: 99%

Mixture in the distribution of haloperidol-induced oral dyskinesias in the rat supports an animal model of tardive dyskinesia

et al. 1998

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Spontaneous adventitious oral movements which are produced in rats by very chronic (6-month) neuroleptic treatment have some phenomenologic and pharmacologic characteristics in common with tardive dyskinesia in humans. However, since not all of the features match, this putative model has been questioned and further support is warranted. Data from several laboratories support dichotomizing these neuroleptic-induced rat oral movements into "low" or "not TD-like" movements and "high" or "TD-like" movements, similar to the division of neuroleptic-induced involuntary movements in humans. Here, we have used mixture analysis to test this proposal statistically in 185 haloperidol-treated and 127 water-treated animals. Rats from several different studies were grouped together to form these two cohorts. The haloperidol dose, route of administration, rating technique, and balanced experimental groups were held constant across all experiments. Results show that two distinct groups of rat movements are induced by very chronic haloperidol treatment (1.5 mg/kg per day). The "low" vacuous chewing movement (VCM) group of rats had an average of 3.6 VCMs/5 min, and the "high" VCM group had an average of 16.1 VCMs/5 min; the control group, with a median VCM rate of 2.0 VCMs/5 min, demonstrated a single distribution. These data suggest that rats, like humans, dichotomize into two groups either expressing or not expressing "high" VCM dyskinesias with very chronic haloperidol treatment.

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“…For example, oral dyskinesias called vacuous chewing movements (VCMs) develop in many, but not all, rats subjected to' chronic treatment with haloperidol, reverse slowly and have some of the pharmacological features of TD (Clow et al, 1980;Gunne et al, 1982;Iversen et al, 1980;Mithani et al, 1987;Tamminga et al, 1990;Waddington, 1990; Waddington et al, 1982). While neuroleptics, administered chronically, are known to alter dopamine D, receptors in the striatum and GABA receptors and ultrastructural features in the substantia nigra (Benes et al, 1983;Gale, 1980;Gunne and Haggstrom, 1983; Gunne et al, 19881, neither of these have been correlated with the behavioral condition (Benes et al, 1983;Burt et al, 1977;Clow et al, 1980;Gale, 1980;Gao et al, 1994; Gunne and Haggstrom, 1983; Gunne et al, 1982; Gunne et al, 1988; Iversen et al, 1980;Mithani et al, 1987;Shirakawa and Tamminga, 1994; Waddington et al, 1982). Other studies have implicated a reduction in GABAergic transmission in the substantia nigra pars reticulata as a putative mechanism to explain neuroleptic induced oral dyskinesias (Gao et al, 1994; Kaneda et al, 1992; Shirakawa and Tamminga, 1994).…”

Section: Introductionmentioning

confidence: 99%

Ultrastructural correlates of haloperidol‐induced oral dyskinesias in rat striatum

Roberts

Gaither

Gao

et al. 1995

Synapse

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Neuroleptics given chronically to rats induce behavioral sequelae which mimic tardive dyskinesia in some respects. The intent of this study was to investigate the ultrastructural correlates of oral dyskinesias (vacuous chewing movements [VCMs]), induced by chronic haloperidol treatment. After 6 months of treatment, rats were divided into low or high VCM groups. Rats in the high VCM group were either sacrificed on drug or were withdrawn from drug for 4 weeks. Ultrastructural analyses of the striatum indicated that synaptic density: 1) was significantly decreased in both the low and high VCM groups compared to normal controls; 2) was more profoundly decreased in the high VCM group as compared to the low VCM group; and 3) recovered to normal following drug withdrawal. Compared to controls, the density of asymmetric synapses was reduced by a similar magnitude in both the low and high VCM groups, suggesting that this change is a result of haloperidol treatment and independent of VCMs. Conversely, the density of symmetric synapses was reduced compared to normal, only in the high VCM group, suggesting that this change is specifically related to the expression of VCMs. In addition, mitochondrial profiles were hypertrophied and less frequent in the high VCM group in comparison to controls; size, but not number, recovered following drug withdrawal. These results identify distinct ultrastructural correlates of chronic haloperidol treatment that are unique to rats that develop VCMs and suggest that these ultrastructural features may play a role in the pathophysiology of oral dyskinesias in rats.

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Tiagabine inhibits haloperidol-induced oral dyskinesias in rats

Cited by 18 publications

References 15 publications

Chronic Olanzapine or Sertindole Treatment Results in Reduced Oral Chewing Movements in Rats Compared to Haloperidol

Chronic Olanzapine or Sertindole Treatment Results in Reduced Oral Chewing Movements in Rats Compared to Haloperidol

Mixture in the distribution of haloperidol-induced oral dyskinesias in the rat supports an animal model of tardive dyskinesia

Ultrastructural correlates of haloperidol‐induced oral dyskinesias in rat striatum

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