Abstract
Background
This study aimed to evaluate the effect of extended olanzapine, clozapine and haloperidol administration on NMDA-R subunit immunoexpression in the rat neocortex and diencephalon.
Methods
To explore NR1, NR2A and NR2B subunit protein expression, densytometric analysis of immunohistochemically stained brain slices was performed.
Results
Interestingly, all neuroleptics caused a downregulation of NMDA-R subunit expression in the thalamus but increased the level of NR1 in the hypothalamus. Olanzapine upregulated hypothalamic NR2A expression, while clozapine and haloperidol decreased hypothalamic levels. We observed no significant changes in NR2B immunoreactivity. None of the studied medications had significant influence on NMDA-R subunit expression in the neocortex.
Conclusions
Neuroleptic-induced reduction in the expression of thalamic NMDA-R subunits may play an important role in the regulation of glutamatergic transmission disorders in cortico–striato–thalamo–cortical loop in schizophrenia. A decrease in NMDA signaling in this region after long-term neuroleptic administration may also cautiously explain the incomplete effectiveness of these drugs in the therapy of schizophrenia-related cognitive disturbances.
This study aimed to evaluate the effect of extended olanzapine, clozapine and haloperidol administration on NMDA-R subunit immunoexpression in the rat neocortex and diencephalon.
Methods
To explore NR1, NR2A and NR2B subunit protein expression, densytometric analysis of immunohistochemically stained brain slices was performed.
Results
Interestingly, all neuroleptics caused a downregulation of NMDA-R subunit expression in the thalamus but increased the level of NR1 in the hypothalamus. Olanzapine upregulated hypothalamic NR2A expression, while clozapine and haloperidol decreased hypothalamic levels. We observed no significant changes in NR2B immunoreactivity. None of the studied medications had significant influence on NMDA-R subunit expression in the neocortex.
Conclusions
Neuroleptic-induced reduction in the expression of thalamic NMDA-R subunits may play an important role in the regulation of glutamatergic transmission disorders in cortico–striato–thalamo–cortical loop in schizophrenia. A decrease in NMDA signaling in this region after long-term neuroleptic administration may also cautiously explain the incomplete effectiveness of these drugs in the therapy of schizophrenia-related cognitive disturbances.
| Original language | English |
|---|---|
| Pages (from-to) | 990–995 |
| Journal | Pharmacological Reports |
| Volume | 68 |
| Issue number | 5 |
| Early online date | 6 Jul 2016 |
| DOIs | |
| Publication status | Published - 1 Oct 2016 |