Blockade of MK-801-Induced Heat Shock Protein 72/73 in Rat Brain by Antipsychotic and Monoaminergic Agents Targeting D2, 5-HT_1A, 5-HT_2A and α₁-Adrenergic Receptors

Title:Blockade of MK-801-Induced Heat Shock Protein 72/73 in Rat Brain by Antipsychotic and Monoaminergic Agents Targeting D2, 5-HT_1A, 5-HT_2A and α₁-Adrenergic Receptors

Volume: 13 Issue: 1

Author(s): Tamara Romon, Anna M. Planas and Albert Adell

Affiliation:

Keywords: MK-801, antipsychotic drugs, dopamine D2 receptor, 5-HT_2A receptor, 5-HT_1A receptor, α₁-adrenoceptor.

Abstract: Noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonists can produce positive and negative symptomatology as well as impairment of cognitive function that closely resemble those present in schizophrenia. In rats, these drugs induce a behavioral syndrome (characterized by hyperlocomotion and stereotypies), an enhanced glutamatergic transmission in the medial prefrontal cortex, and damage to retrosplenial cortical neurons in adult rats, which was measured as the induction of the stress protein 72/73 kDa heat shock protein (Hsp72/73). In the present work, we have examined the existence of possible differences among different antipsychotic drugs in their capacity to block immunolabeling of Hsp72/73 in the retrosplenial cortex of the rat induced by the potent NMDA receptor antagonist, MK- 801. In addition, the effects of selective monoaminergic agents were also studied to delineate the particular receptors responsible for the actions of antipsychotic drugs. Pretreatment with clozapine, chlorpromazine, olanzapine, ziprasidone - and to a lesser extent haloperidol-reduced the formation of Hsp72/73 protein in the rat retrosplenial cortex after the administration of MK-801. In addition, antagonism at dopamine D2 (raclopride), 5-HT_2A (M100907) and α1- adrenoceptors (prazosin) as well as agonism at 5-HT_1A receptors (BAY x 3702) also diminished the MK-801-induced number of cells labeled with Hsp72/73. Each of these effects may contribute to antipsychotic action. The results suggest that the efficacy of atypical antipsychotic drugs in the clinic may result from a combined effect on 5-HT_2A, 5-HT_1A and α₁-adrenergic receptors added to the classical dopamine D2 receptor antagonism.

Cite this article as:

Romon Tamara, Planas M. Anna and Adell Albert, Blockade of MK-801-Induced Heat Shock Protein 72/73 in Rat Brain by Antipsychotic and Monoaminergic Agents Targeting D2, 5-HT_1A, 5-HT_2A and α₁-Adrenergic Receptors, CNS & Neurological Disorders - Drug Targets 2014; 13 (1) . https://dx.doi.org/10.2174/18715273113129990110