Ketamine modulates behavioral and neurochemical alterations induced by stress:
novel evidence for treatment of mood disorders
Gislaine Z. Réus1,2*, Marcos Paulo Nacif1, Helena M. Abelaira1, Débora B. Tomaz1,
Maria Augusta B. dos Santos1, Anelise S. Carlessi1, Gabriela C. Jeremias3, Giselli
Scaini3, Meline O.S. Morais3, Renata C. Gonçalves4, Francieli Vuolo4, Felipe DalPizzol4, Emilio L. Streck3, and João Quevedo1,2
1
Laboratório de Neurociências, Programa de Pós-Graduação em Ciências da Saúde,
Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense,
Criciúma, SC, Brazil;
2
Center for Experimental Models in Psychiatry, Department of Psychiatry and
Behavioral Sciences, Medical School, The University of Texas Health Science Center at
Houston, Houston, TX, USA;
3
Laboratório de Bioenergética, Programa de Pós-Graduação em Ciências da Saúde,
Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense,
Criciúma, SC, Brazil;
4
Laboratório de Fisiopatologia Experimental, Programa de Pós-Graduação em Ciências
da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul
Catarinense, Criciúma, SC, Brazil.
*Corresponding author:
Prof. Gislaine Z. Réus, PhD
Laboratório de Neurociências,
Programa de Pós-Graduação em Ciências da Saúde,
Unidade Acadêmica de Ciências da Saúde,
Universidade do Extremo Sul Catarinense,
88806-000 Criciúma, SC, Brazil
Fax: +55 48 3431-2736.
E-mail: [email protected]
Abstract
Introduction: A growing body of evidence is pointing towards an association between
glutamatergic system within depression and bipolar disorder (BD). Objective: The
present study was aimed to evaluate the behavioral and molecular effects of the
ketamine, an antagonist of NMDA receptor of glutamate in maternally deprived adult
rats. Results: In deprived rats treated with saline, it was observed an increase in the
immobility time, but ketamine treatment reversed this effect. In the amygdala and
nucleus accumbens (NAc) of deprived rats there was a decrease on BDNF, however,
ketamine was able to reverse this alteration. The complex I was reduced in the
prefrontal cortex (PF) and amygdala of deprived rats, the complex II-III was reduced in
the PF and hippocampus of deprived rats. The ketamine treatment increased the
complex IV in the PF and amygdala of deprived rats. The creatine kinase was decreased
in the PF and amygdala of deprived rats, but ketamine treatment reversed this effect in
the amygdala. Ketamine reduced TNF-α, IL-1 and -6 in the serum and CSF of deprived
rats. Conclusion: In conclusion, these findings further support a relationship between
immune activation, alteration on neurotrophins, energy metabolism, and depression, and
considering the action of ketamine, it is suggested that antagonists of NMDA receptor
could exert their effects by modulating of immune system, BDNF and energy
metabolism.
Keywords: Ketamine; NMDA receptor; BDNF; energy metabolism; cytokine.