RT Journal Article
T1 A correlation of haloperidol-induced cognitive deficit with dysfunctional dopamine receptor activity in nonhuman primate.
A1 Navarro-Lobato, Irene
A1 Masmudi-Martín, Mariam
A1 López-Aranda, Manuel Francisco
A1 López-Téllez, Juan Félix
A1 Khan, Zafar U.
K1 Primates
K1 Cerebro - Efectos de los medicamentos
K1 Antagonistas de la dopamina
K1 Haloperidol
K1 Receptores de dopamina
AB Haloperidol is an antipsychotic drug that acts through blockage of dopamine D2 receptors. Chronic administration of this antipsychotic drug in nonhuman primates induces a pronounced cognitive deficit. However, receptor subtypes that are responsible for this cognitive dysfunction remain unknown. Therefore, brains of chronic haloperidol-treated young and aged monkeys were used to analyze the intricate relation of receptor activity, cognitive dysfunction, and haloperidol-mediated actions in the production of harmful effects. Taking into account the significant cognitive loss observed after haloperidol treatment, it was predicted that changes in the cognitive status that correlate with the receptor activity in the prefrontal cortex and striatum, areas implicated in the processing of haloperidol-mediated effects in brain, should be common in both young and aged animals. Based on this concept, we observed that in the prefrontal cortex, dopamine D1 and D2 receptors showed changes in receptor levels that were common in both age groups. However, this relationship was absent in GABAA, serotonin 5HT2 and muscaranic receptors. In contrast to the prefrontal cortex, in striatum, this change was restricted to the dopamine D2 receptors only. Therefore, from our results, it seems that apart from the downregulation of D1 receptor activity in the prefrontal cortex, an upregulation of D2 receptors could also contribute to the generation of the cognitive loss observed in haloperidol-treated monkeys. Additionally, reduced excitatory input due to hampered cortico-striatal D1 dopaminergic activity and stronger inhibition at the synapse of excitatory input site by upregulated striatal D2 receptor activity could promote the side effects associated with haloperidol.
PB Dovepress
YR 2010
FD 2010-05-04
LK https://hdl.handle.net/10630/38605
UL https://hdl.handle.net/10630/38605
LA eng
NO Navarro-Lobato I, Masmudi-Martín M, López-Aranda MF, López-Téllez JF, Khan ZU. A correlation of haloperidol-induced cognitive deficit with dysfunctional dopamine receptor activity in nonhuman primate. Open Access Animal Physiology. 2010;2:1-8 https://doi.org/10.2147/OAAP.S7262
NO This work was supported financially by Ministerio de Ciencia e Innovacion grant BFU 06-0306 and a Junta de Andalucia grant CTS 586/08
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 12 abr 2026