Upregulation of heat-shock protein HSP-70 and glutamate transporter-1/glutamine synthetase in the striatum and hippocampus in haloperidol-induced dopamine-supersensitivity-state rats.
Pharmacol Biochem Behav
; 211: 173288, 2021 12.
Article
em En
| MEDLINE
| ID: mdl-34653399
ABSTRACT
BACKGROUND:
The excessive blockade of dopamine D2 receptors (DRD2s) with long-term antipsychotic treatment is known to induce a dopamine supersensitivity state (DSS). The mechanism of DSS is speculated to be a compensatory up-regulation of DRD2s, but an excess blockade of DRD2s can also cause glutamatergic neuronal damage. Herein, we investigated whether antipsychotic-induced neuronal damage plays a role in the development of DSS.METHODS:
Haloperidol (HAL; 0.75 mg/kg/day for 14 days) or vehicle was administered to rats via an osmotic mini-pump. Haloperidol-treated rats were divided into groups of DSS rats and non-DSS rats based on their voluntary locomotion data. We then determined the tissue levels of glutamate transporter-1 (GLT-1)/glutamine synthetase (GS) and heat shock protein-70 (HSP-70) in the rats' brain regions.RESULTS:
The levels of HSP-70 in the striatum and CA-3 region of the DSS rats were significantly higher than those of the control and non-DSS rats, whereas the dentate gyrus HSP-70 levels in both the DSS and non-DSS rats were increased versus the controls. The levels of GLT-1/GS in the CA-3 and nucleus accumbens were increased in the DSS rats.CONCLUSIONS:
These results suggest that the DSS rats experienced striatal neuronal damage and indicate that a HAL-induced upregulation of HSP-70 and the GLT-1/GS system in the CA3 may be involved in the development of DSS. It remains unknown why the non-DSS rats did not suffer neuronal damage. In view of the need for therapeutic strategies for treatment-resistant schizophrenia, dopamine supersensitivity psychosis, and tardive dyskinesia, further investigations of our findings are warranted.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Encéfalo
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Dopamina
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Proteínas de Choque Térmico HSP70
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Transportador 2 de Aminoácido Excitatório
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Glutamato-Amônia Ligase
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Haloperidol
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article