Prefrontal activity decline in women under a single dose of diazepam during rule-guided responses: an fMRI study
Daily life events confront us with new situations demanding responses to usual and unusual rules. Diazepam (DZ), a clinically important drug, facilitates the inhibitory activity of the GABAergic system. Prefrontal cortex, rich in DZ receptors, coordinates necessary resources to direct actions according to rules. The balance between excitatory and inhibitory activity is critical to achieve optimal function of brain systems leading to complex functions. Major sex differences in the physiological mechanisms of the GABAergic system have been reported. However, the differential influence of DZ on men and women in neural activity during behavior directed by frontal lobes remains unexplored. The ability of healthy volunteers to select responses following usual/congruent and novel/incongruent rules, and brain correlates were measured with fMRI under the administration of DZ and a placebo. 10 mg of DZ was enough to decrease the performance in a different manner between men and women. While reaction times increased in both men and women, women committed more errors selecting responses than men under DZ. Men demonstrated increased activity, while women demonstrated decreased activity in frontal regions involved in response selection of rules. These findings could have important consequences in understanding the differential influences of DZ between the sexes in complex daily life situations. More importantly, this study emphasizes the importance of understanding the differential effects on men and women of drugs widely employed by society, thereby achieves better therapeutic results and avoids side effects that the present study revealed to be different between sexes.
KeywordsBenzodiazepine Diazepam Sex differences fMRI Rule-guided behavior Frontal lobes
We are very grateful to Madalyn Marabella for correcting the English version of the manuscript. This work was supported by CONACYT, Project: 50709. Z. Muñoz-Torres received a grant from CONACYT. This work constitutes part of an academic thesis of the Biomedical Science Ph.D. program at UNAM. We thank Dr. Julian A. Sanchez Cortazar of Aceleracion Nuclear y Resonancia Magnetica S.A. de C.V.; Dr. Bernardo Ronzon Fernandez, and QFB Alma Delia Guerrero Huesca at Laboratorio y Banco de Sangre for the facilities of fMRI and blood analyses at Hospital Angeles del Pedregal.
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